CeLLaTe Datasets
Collection
Root version of CeLLaTe. Best represents curation guides set out for CeLLaTe prior to any testing / edits of data during model production. • 8 items • Updated
PMCID stringclasses 34
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PMC12479362 | A single-cell and spatial genomics atlas of human skin fibroblasts reveals shared disease-related fibroblast subtypes across tissues
Source paper: PMC12479362 | [{'end': 66, 'label': 'CellType', 'start': 50, 'text': 'skin fibroblasts'}
{'end': 108, 'label': 'CellType', 'start': 98, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Fibroblasts sculpt the architecture and cellular microenvironments of various tissues. | [{'end': 11, 'label': 'CellType', 'start': 0, 'text': 'Fibroblasts'}] | Single_Cell |
PMC12479362 | Here we constructed a spatially resolved atlas of human skin fibroblasts from healthy skin and 23 skin diseases, with comparison to 14 cross-tissue diseases. | [{'end': 90, 'label': 'Tissue', 'start': 86, 'text': 'skin'}
{'end': 72, 'label': 'CellType', 'start': 50, 'text': 'human skin fibroblasts'}] | Single_Cell |
PMC12479362 | We define six major skin fibroblast subtypes in health and three that are disease-specific. | [{'end': 35, 'label': 'CellType', 'start': 20, 'text': 'skin fibroblast'}] | Single_Cell |
PMC12479362 | We characterize two fibroblast subtypes further as they are conserved across tissues and are immune-related. | [{'end': 30, 'label': 'CellType', 'start': 20, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | The first, F3: fibroblastic reticular cell-like fibroblast ( CCL19 CD74 HLA-DRA ), is a fibroblastic reticular cell-like subtype that is predicted to maintain the superficial perivascular immune niche. | [{'end': 25, 'label': 'CellType', 'start': 15, 'text': 'fibroblast'}
{'end': 115, 'label': 'CellType', 'start': 88, 'text': 'fibroblastic reticular cell'}
{'end': 200, 'label': 'Tissue', 'start': 175, 'text': 'perivascular immune niche'}] | Single_Cell |
PMC12479362 | The second, F6: inflammatory myofibroblasts ( IL11 MMP1 CXCL8 IL7R ), characterizes early human skin wounds, inflammatory diseases with scarring risk and cancer. | [{'end': 43, 'label': 'CellType', 'start': 29, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | F6: inflammatory myofibroblasts were predicted to recruit neutrophils, monocytes and B cells across multiple human tissues. | [{'end': 80, 'label': 'CellType', 'start': 71, 'text': 'monocytes'}
{'end': 69, 'label': 'CellType', 'start': 58, 'text': 'neutrophils'}
{'end': 92, 'label': 'CellType', 'start': 85, 'text': 'B cells'}
{'end': 31, 'label': 'CellType', 'start': 17, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | Our study provides a harmonized nomenclature for skin fibroblasts in health and disease, contextualized with cross-tissue findings and clinical skin disease profiles. | [{'end': 65, 'label': 'CellType', 'start': 49, 'text': 'skin fibroblasts'}] | Single_Cell |
PMC12479362 | Fibroblasts are crucial cells for shaping tissue architecture and immune cell niches . | [{'end': 11, 'label': 'CellType', 'start': 0, 'text': 'Fibroblasts'}] | Single_Cell |
PMC12479362 | Studying the heterogeneity of fibroblast subtypes has been challenging due to the scarcity of unique surface markers and their tendency to adopt activated phenotypes during in vitro culture . | [{'end': 40, 'label': 'CellType', 'start': 30, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics technologies have overcome these challenges, enabling the dissection of fibroblast heterogeneity in human tissues . | [] | Single_Cell |
PMC12479362 | While recent studies have described fibroblast states in human skin, they have not spatially resolved their tissue microanatomical location. | [{'end': 67, 'label': 'Tissue', 'start': 57, 'text': 'human skin'}] | Single_Cell |
PMC12479362 | Very few, if any, have interrogated fibroblasts in diverse disease conditions in the skin and across human tissues . | [{'end': 47, 'label': 'Tissue', 'start': 36, 'text': 'fibroblasts'}
{'end': 89, 'label': 'Tissue', 'start': 85, 'text': 'skin'}] | Single_Cell |
PMC12479362 | Consequently, the fibroblast composition and function in human skin; how it changes across a range of diseases (inflammatory, cancer and fibrosis/scarring); and how these populations relate to other human tissues is still unclear. | [{'end': 67, 'label': 'Tissue', 'start': 57, 'text': 'human skin'}] | Single_Cell |
PMC12479362 | In this study, we integrated published large-scale scRNA-seq datasets of healthy human skin and 23 skin diseases and generated spatial transcriptomics data from two different modalities to construct a high-resolution spatially resolved atlas of more than 350,000 adult human skin fibroblasts. | [{'end': 91, 'label': 'Tissue', 'start': 81, 'text': 'human skin'}
{'end': 291, 'label': 'CellType', 'start': 275, 'text': 'skin fibroblasts'}] | Single_Cell |
PMC12479362 | We provide a consensus annotation of skin fibroblasts based on gene expression profiles and spatial locations, and contextualize these findings with fibroblast data from other healthy and diseased human tissues. | [{'end': 53, 'label': 'CellType', 'start': 37, 'text': 'skin fibroblasts'}] | Single_Cell |
PMC12479362 | Our scRNA-seq and spatial datasets resources are freely available for download and interactive data exploration at https://cellatlas.io/studies/skin-fibroblast . | [] | Single_Cell |
PMC12479362 | We re-processed and integrated 2.1 million cells from scRNA-seq data of adult human skin, comprising 32 datasets and 251 donors (Fig. 1a and Supplementary Table 1 ) using single-cell variational inference (scVI) ( Methods ) . | [{'end': 88, 'label': 'Tissue', 'start': 78, 'text': 'human skin'}] | Single_Cell |
PMC12479362 | After quality control, 357,276 high-quality fibroblasts were selected based on canonical marker gene expression (Fig. 1a and Extended Data Fig. 1a ). | [{'end': 55, 'label': 'CellType', 'start': 44, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | In healthy skin, we identified six major fibroblast subtypes based on differential gene expression (Supplementary Data Fig. 1a and Supplementary Table 2 ) and pathway enrichment analysis (Extended Data Fig. 2a and Methods ). | [{'end': 51, 'label': 'CellType', 'start': 41, 'text': 'fibroblast'}
{'end': 15, 'label': 'Tissue', 'start': 11, 'text': 'skin'}] | Single_Cell |
PMC12479362 | The six fibroblast subtypes were observed across different covariates (Extended Data Fig. 1b–g and Supplementary Note 1 ). | [{'end': 18, 'label': 'CellType', 'start': 8, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Complementary spatial transcriptomic methods validated the presence of each of the six fibroblast subtypes and revealed their distinct microanatomical locations (Fig. 2a–c , Extended Data Figs. 3 and 4 and Supplementary Fig. 2 ). | [{'end': 97, 'label': 'CellType', 'start': 87, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Two of the six fibroblast populations (F1: superficial (papillary) and F2: universal (reticular)) were uniformly present throughout skin at different tissue depths. | [{'end': 136, 'label': 'Tissue', 'start': 132, 'text': 'skin'}
{'end': 25, 'label': 'CellType', 'start': 15, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | F1: superficial (papillary) fibroblasts localized adjacent to the skin epithelium in the papillary dermis (Fig. 2b,c ) and expressed genes encoding superficial dermal collagens ( COL13A1 , COL18A1 and COL23A1 ) and Wnt signaling inhibitors ( APCDD1 , WIF1 and NKD2 ) (Fig. 1c ). | [{'end': 39, 'label': 'CellType', 'start': 4, 'text': 'superficial (papillary) fibroblasts'}
{'end': 81, 'label': 'Tissue', 'start': 66, 'text': 'skin epithelium'}
{'end': 105, 'label': 'Tissue', 'start': 89, 'text': 'papillary dermis'}] | Single_Cell |
PMC12479362 | A Wnt-mediated synergistic interplay between superficial dermal fibroblasts and basal epithelial cells has been reported to reciprocally maintain cellular identity . | [{'end': 75, 'label': 'CellType', 'start': 45, 'text': 'superficial dermal fibroblasts'}
{'end': 102, 'label': 'CellType', 'start': 80, 'text': 'basal epithelial cells'}] | Single_Cell |
PMC12479362 | F2: universal (reticular) fibroblasts were located deeper in the skin, interspersed between large collagen fibers in the reticular dermis (Fig. 2b,c ). | [{'end': 69, 'label': 'Tissue', 'start': 65, 'text': 'skin'}
{'end': 37, 'label': 'CellType', 'start': 4, 'text': 'universal (reticular) fibroblasts'}
{'end': 137, 'label': 'Tissue', 'start': 121, 'text': 'reticular dermis'}] | Single_Cell |
PMC12479362 | This population was characterized by high expression of marker genes of universal PI16 fibroblasts ( PI16 , CD34 and MFAP5) , a fibroblast subtype found in many human tissues and postulated to represent a precursor fibroblast cell state . | [{'end': 98, 'label': 'CellType', 'start': 72, 'text': 'universal PI16 fibroblasts'}
{'end': 138, 'label': 'CellType', 'start': 128, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Transcription factor activity inference identified KLF5 in F2: universal fibroblasts (Extended Data Fig. 2b ), which has been reported to drive the universal Pi16 state . | [{'end': 84, 'label': 'CellType', 'start': 63, 'text': 'universal fibroblasts'}] | Single_Cell |
PMC12479362 | As fascial fibroblasts (F_Fascia) are proposed as a potential progenitor cell in mouse skin , we included these cells in an additional integration, identifying that F_Fascia formed a subset of F2: universal (Extended Data Fig. 1i,j and Supplementary Note 2 ). | [{'end': 33, 'label': 'CellType', 'start': 3, 'text': 'fascial fibroblasts (F_Fascia)'}
{'end': 91, 'label': 'Tissue', 'start': 81, 'text': 'mouse skin'}
{'end': 173, 'label': 'CellType', 'start': 165, 'text': 'F_Fascia'}
{'end': 77, 'label': 'CellType', 'start': 62, 'text': 'progenitor cell'}] | Single_Cell |
PMC12479362 | The remaining fibroblast subsets were more focal in localization, being associated with vascular or adnexal structures. | [{'end': 24, 'label': 'CellType', 'start': 14, 'text': 'fibroblast'}
{'end': 118, 'label': 'Tissue', 'start': 88, 'text': 'vascular or adnexal structures'}] | Single_Cell |
PMC12479362 | We thus used hematoxylin and eosin (H&E) staining to illustrate these microenvironments. | [] | Single_Cell |
PMC12479362 | F3: fibroblastic reticular cell (FRC)-like fibroblasts were located predominantly in the superficial perivascular region in proximity to immune cells (Fig. 2b and Extended Data Figs. 3a,b and 4a,b ). | [{'end': 54, 'label': 'CellType', 'start': 4, 'text': 'fibroblastic reticular cell (FRC)-like fibroblasts'}
{'end': 120, 'label': 'Tissue', 'start': 89, 'text': 'superficial perivascular region'}
{'end': 149, 'label': 'CellType', 'start': 137, 'text': 'immune cells'}] | Single_Cell |
PMC12479362 | F3: FRC-like fibroblasts transcriptomically resembled FRCs, which are specialized fibroblasts found in lymphoid organs/structures that maintain immune niches (Extended Data Fig. 1h ) , expressing genes that attract and compartmentalize immune cells ( CCL19 , CXCL12 and CH25H ), maintain immune cell survival and functio... | [{'end': 24, 'label': 'CellType', 'start': 4, 'text': 'FRC-like fibroblasts'}
{'end': 58, 'label': 'CellType', 'start': 54, 'text': 'FRCs'}
{'end': 93, 'label': 'CellType', 'start': 82, 'text': 'fibroblasts'}
{'end': 129, 'label': 'Tissue', 'start': 103, 'text': 'lymphoid organs/structures'}
{'end': 157, 'label': '... | Single_Cell |
PMC12479362 | F2/3: perivascular fibroblasts also localized with immune cells but, unlike F3: FRC-like fibroblasts, were additionally enriched in deep perivascular regions and other sites (Fig. 2a–c and Extended Data Fig. 4b,c ). | [{'end': 63, 'label': 'CellType', 'start': 51, 'text': 'immune cells'}
{'end': 30, 'label': 'CellType', 'start': 6, 'text': 'perivascular fibroblasts'}
{'end': 100, 'label': 'CellType', 'start': 80, 'text': 'FRC-like fibroblasts'}] | Single_Cell |
PMC12479362 | A fraction of F2/3: perivascular fibroblasts showed elevated expression of PPARG (Fig. 1c ) and pathway analysis suggested a role in adipocyte differentiation (Extended Data Fig. 2a ). | [{'end': 44, 'label': 'CellType', 'start': 20, 'text': 'perivascular fibroblasts'}] | Single_Cell |
PMC12479362 | The capability to differentiate into adipocytes is characteristic of the reticular fibroblast (equivalent to F2: universal) lineage . | [{'end': 47, 'label': 'CellType', 'start': 37, 'text': 'adipocytes'}
{'end': 93, 'label': 'CellType', 'start': 73, 'text': 'reticular fibroblast'}] | Single_Cell |
PMC12479362 | F2/3: perivascular fibroblasts shared select gene expression with both F2: universal and F3: FRC-like fibroblasts (Fig. 3c ). | [{'end': 30, 'label': 'CellType', 'start': 6, 'text': 'perivascular fibroblasts'}
{'end': 113, 'label': 'CellType', 'start': 93, 'text': 'FRC-like fibroblasts'}] | Single_Cell |
PMC12479362 | F4: hair follicle-associated fibroblasts ( ASPN COL11A1 ) encompassed three subclusters that were associated with specific regions of the hair follicle (Fig. 2b,c ). | [{'end': 151, 'label': 'Tissue', 'start': 138, 'text': 'hair follicle'}
{'end': 40, 'label': 'CellType', 'start': 29, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | The first is a well-characterized dermal sheath (DS) population (F4: DS_DPEP1 ) that wraps around the lower/mid hair follicle (Fig. 2b ). | [{'end': 125, 'label': 'Tissue', 'start': 112, 'text': 'hair follicle'}
{'end': 63, 'label': 'CellType', 'start': 34, 'text': 'dermal sheath (DS) population'}] | Single_Cell |
PMC12479362 | The second is a novel F4: TNN COCH subtype, expressing tendon-associated genes ( MKX and TNMD ) and observed at the isthmus (mid-hair shaft) (Fig. 2b and Extended Data Fig. 4d ). | [{'end': 140, 'label': 'Tissue', 'start': 116, 'text': 'isthmus (mid-hair shaft)'}
{'end': 42, 'label': 'CellType', 'start': 26, 'text': 'TNN COCH subtype'}] | Single_Cell |
PMC12479362 | The third F4: DP_HHIP subtype uniquely expressed dermal papilla marker genes ( CORIN , HHIP , RSPO3 and LEF1 ) . | [{'end': 29, 'label': 'CellType', 'start': 14, 'text': 'DP_HHIP subtype'}] | Single_Cell |
PMC12479362 | F5: Schwann-like fibroblasts (SCN7A, FMO2 , FGFBP2 and OLFML2A ) contained two subclusters (F5: NGFR and F5: RAMP1 ) (Extended Data Fig. 1k ) . | [{'end': 28, 'label': 'CellType', 'start': 4, 'text': 'Schwann-like fibroblasts'}
{'end': 100, 'label': 'CellType', 'start': 92, 'text': 'F5: NGFR'}
{'end': 114, 'label': 'CellType', 'start': 105, 'text': 'F5: RAMP1'}] | Single_Cell |
PMC12479362 | F5: RAMP1 fibroblasts were enriched near innervated eccrine glands and expressed genes encoding the receptor complex for the neuropeptide CGRP (Fig. 2b,c and Extended Data Figs. 1l , 3c,d and 4c ), suggesting a possible interface with the nervous system. | [{'end': 253, 'label': 'Tissue', 'start': 239, 'text': 'nervous system'}
{'end': 21, 'label': 'CellType', 'start': 4, 'text': 'RAMP1 fibroblasts'}
{'end': 66, 'label': 'Tissue', 'start': 41, 'text': 'innervated eccrine glands'}] | Single_Cell |
PMC12479362 | F5: NGFR colocalized with Schwann cells, suggesting that they are a nerve-associated population. | [{'end': 8, 'label': 'CellType', 'start': 0, 'text': 'F5: NGFR'}
{'end': 39, 'label': 'CellType', 'start': 26, 'text': 'Schwann cells'}
{'end': 95, 'label': 'CellType', 'start': 68, 'text': 'nerve-associated population'}] | Single_Cell |
PMC12479362 | Fibroblasts have been described in the endoneurium and perineurium of nerve fibers from imaging studies , and ‘Schwann-like fibroblasts’ have recently been reported in human skin scRNA-seq data . | [{'end': 11, 'label': 'Tissue', 'start': 0, 'text': 'Fibroblasts'}
{'end': 50, 'label': 'Tissue', 'start': 39, 'text': 'endoneurium'}
{'end': 82, 'label': 'Tissue', 'start': 70, 'text': 'nerve fibers'}
{'end': 135, 'label': 'CellType', 'start': 111, 'text': 'Schwann-like fibroblasts'}] | Single_Cell |
PMC12479362 | We confirmed that our six fibroblast subtypes were distinct from Schwann cells and pericytes (Extended Data Fig. 1j,k and Supplementary Note 2 ). | [{'end': 92, 'label': 'CellType', 'start': 83, 'text': 'pericytes'}
{'end': 36, 'label': 'CellType', 'start': 26, 'text': 'fibroblast'}
{'end': 78, 'label': 'CellType', 'start': 65, 'text': 'Schwann cells'}] | Single_Cell |
PMC12479362 | In addition, we harmonized our skin fibroblast annotation with a previous classification (Supplementary Data Fig. 1b ). | [] | Single_Cell |
PMC12479362 | Overall, we provide a new framework for healthy human skin fibroblast annotation based on gene expression profiles (Fig. 1 ) and spatial location (Fig. 2 ) that integrates previous fibroblast descriptions in skin and across tissues. | [{'end': 212, 'label': 'Tissue', 'start': 208, 'text': 'skin'}] | Single_Cell |
PMC12479362 | Our findings of transcriptionally defined fibroblast subtypes in distinct microanatomical locations suggest a role for regional fibroblasts in supporting distinct niche functions. | [{'end': 52, 'label': 'CellType', 'start': 42, 'text': 'fibroblast'}
{'end': 99, 'label': 'Tissue', 'start': 74, 'text': 'microanatomical locations'}
{'end': 139, 'label': 'CellType', 'start': 128, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | We next sought to identify how fibroblast states change in diseased skin. | [{'end': 72, 'label': 'Tissue', 'start': 68, 'text': 'skin'}] | Single_Cell |
PMC12479362 | We used scPoli , a deep-learning model for integration and identification of novel cell states in single-cell transcriptome data ( Methods ) (Fig. 3a ). | [] | Single_Cell |
PMC12479362 | We mapped fibroblasts from skin diseases to our healthy/nonlesional F1–F5 fibroblast reference. | [{'end': 21, 'label': 'CellType', 'start': 10, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | Out of 190,756 fibroblasts from diseased states, 121,167 diseased cells were confidently assigned existing F1–F5 cell labels (Extended Data Fig. 5a,b ). | [{'end': 26, 'label': 'CellType', 'start': 15, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | The remaining 69,589 fibroblasts from the disease data were classified as uncertain (unlabeled) by scPoli (Fig. 3b ). | [{'end': 32, 'label': 'CellType', 'start': 21, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | Manual annotation based on differential gene expression (Supplementary Data Fig. 1c and Supplementary Table 3 ) and pathway analysis (Extended Data Fig. 5c ) revealed two ‘disease-adapted’ and three ‘disease-specific’ fibroblast subtypes (Fig. 3b–f ). | [{'end': 228, 'label': 'CellType', 'start': 218, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | ‘Disease-adapted’ fibroblasts resembled a healthy fibroblast subtype counterpart (Fig. 3e ) and were expanded in disease settings (Fig. 3d ). | [{'end': 29, 'label': 'CellType', 'start': 18, 'text': 'fibroblasts'}
{'end': 60, 'label': 'CellType', 'start': 50, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | The first disease-adapted fibroblast subtype resembled F1: superficial fibroblasts in healthy skin (Fig. 3e ). | [{'end': 36, 'label': 'CellType', 'start': 26, 'text': 'fibroblast'}
{'end': 82, 'label': 'CellType', 'start': 71, 'text': 'fibroblasts'}
{'end': 98, 'label': 'Tissue', 'start': 94, 'text': 'skin'}] | Single_Cell |
PMC12479362 | The F1-like disease population upregulated genes suggestive of regenerative function ( CRABP1 , CYP26B1 and WNT5A ) . | [] | Single_Cell |
PMC12479362 | CRABP1 and CYP26B1 are markers of superficial/upper wound fibroblasts in mice , which are thought to be the source of wound-induced hair follicle neogenesis , and involved in retinoic acid degradation. | [{'end': 69, 'label': 'CellType', 'start': 58, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | CRABP1 fibroblasts are also associated with regeneration in reindeer skin and early-gestational human skin . | [{'end': 18, 'label': 'CellType', 'start': 0, 'text': 'CRABP1 fibroblasts'}
{'end': 73, 'label': 'Tissue', 'start': 60, 'text': 'reindeer skin'}
{'end': 106, 'label': 'Tissue', 'start': 96, 'text': 'human skin'}] | Single_Cell |
PMC12479362 | The second disease-adapted fibroblast subtype resembled F3: FRC-like fibroblasts and upregulated CXCL9 and/or ADAMDEC1 (Fig. 3e ). | [{'end': 37, 'label': 'CellType', 'start': 27, 'text': 'fibroblast'}
{'end': 80, 'label': 'CellType', 'start': 60, 'text': 'FRC-like fibroblasts'}] | Single_Cell |
PMC12479362 | CXCL9 is a chemoattractant for CXCR3 cells and has been reported as an activation marker for FRCs in lymphoid tissues . | [{'end': 117, 'label': 'Tissue', 'start': 101, 'text': 'lymphoid tissues'}
{'end': 42, 'label': 'CellType', 'start': 31, 'text': 'CXCR3 cells'}
{'end': 97, 'label': 'CellType', 'start': 93, 'text': 'FRCs'}] | Single_Cell |
PMC12479362 | ‘Disease-specific’ fibroblasts (F6: inflammatory myofibroblasts, F7: myofibroblasts and F8: fascia-like myofibroblasts) did not have a healthy skin fibroblast counterpart and highly expressed a myofibroblast gene signature. | [{'end': 30, 'label': 'CellType', 'start': 19, 'text': 'fibroblasts'}
{'end': 158, 'label': 'CellType', 'start': 143, 'text': 'skin fibroblast'}
{'end': 63, 'label': 'CellType', 'start': 49, 'text': 'myofibroblasts'}
{'end': 83, 'label': 'CellType', 'start': 69, 'text': 'myofibroblasts'}
{'end': 118, 'label': 'Cell... | Single_Cell |
PMC12479362 | This myofibroblast signature included contractility ( ACTA2 ), extracellular matrix (ECM) ( COL3A1 , COL5A1 , COL8A1 , POSTN and CTHRC1 ) and other myofibroblast-associated genes ( LRRC15 , SFRP4 , ASPN , RUNX2 and SCX ) (Fig. 3c,g and Extended Data Fig. 5d,e ) . | [] | Single_Cell |
PMC12479362 | F6: inflammatory myofibroblasts additionally expressed immune-related genes such as interleukins ( IL11 and IL24 ), chemokines ( CXCL5 , CXCL8 , CXCL13 and CCL11 ) and matrix metalloproteinases that can remodel tissue to facilitate immune cell infiltration ( MMP1 ) (Fig. 3c ). | [{'end': 31, 'label': 'CellType', 'start': 17, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | JAK–STAT and hypoxic signaling genes were also elevated (Fig. 3h ). | [] | Single_Cell |
PMC12479362 | F7: myofibroblasts and F8: fascia-like myofibroblasts were distinguished by a higher expression of ECM and TGFβ signaling genes, as well as the mechanotransducer PIEZO2 (Fig. 3c,h ). | [{'end': 18, 'label': 'CellType', 'start': 4, 'text': 'myofibroblasts'}
{'end': 53, 'label': 'CellType', 'start': 39, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | F8: fascia-like myofibroblasts were distinguished by expression of F_Fascia-associated genes (Fig. 3c ). | [{'end': 30, 'label': 'CellType', 'start': 16, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | Overall, our results indicate that healthy fibroblasts can acquire a regenerative phenotype in F1: superficial fibroblasts ( CRABP1 CYP27B1 ), a distinct polarization in F3: FRC-like fibroblasts ( CXCL9 / ADAMDEC1 ) and potentially give rise to myofibroblast states ( ACTA2 COL8A1 SFRP4 ) in diseased skin. | [{'end': 54, 'label': 'CellType', 'start': 43, 'text': 'fibroblasts'}
{'end': 258, 'label': 'CellType', 'start': 245, 'text': 'myofibroblast'}
{'end': 305, 'label': 'Tissue', 'start': 301, 'text': 'skin'}
{'end': 122, 'label': 'CellType', 'start': 111, 'text': 'fibroblasts'}
{'end': 194, 'label': 'CellType', 'start... | Single_Cell |
PMC12479362 | We next leveraged the diverse clinical profiles of skin diseases to assess whether fibroblast subtypes provide molecular insights into disease endotypes with respect to scarring. | [{'end': 93, 'label': 'CellType', 'start': 83, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | We assigned the 23 skin diseases into three clinically determined risk of scarring groups: low scarring risk, moderate scarring risk, and established scarring/fibrosis (see Methods ) (Fig. 4a ). | [] | Single_Cell |
PMC12479362 | We excluded neurofibroma from this analysis as it was the only case of benign neoplasia, consisting primarily of F5: Schwann-like and F2/3: perivascular fibroblasts (Extended Data Fig. 6a ). | [{'end': 129, 'label': 'CellType', 'start': 117, 'text': 'Schwann-like'}
{'end': 164, 'label': 'CellType', 'start': 153, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | We identified distinct fibroblast compositions for each scarring risk category (Fig. 4b ). | [] | Single_Cell |
PMC12479362 | Low scarring risk diseases were characterized by a high prevalence of F1: superficial ( CRABP CYP27B1 ) and F3: FRC-like fibroblasts ( CXCL9 / ADAMDEC1 ) (Fig. 4b ), without notable F6–F8 myofibroblast populations. | [{'end': 132, 'label': 'CellType', 'start': 112, 'text': 'FRC-like fibroblasts'}
{'end': 201, 'label': 'CellType', 'start': 188, 'text': 'myofibroblast'}] | Single_Cell |
PMC12479362 | This finding agrees with the regenerative-associated gene profile of disease-associated F1: superficial fibroblasts and a role for F3: FRC-like fibroblasts in maintaining immune niches. | [{'end': 115, 'label': 'CellType', 'start': 104, 'text': 'fibroblasts'}
{'end': 155, 'label': 'CellType', 'start': 135, 'text': 'FRC-like fibroblasts'}] | Single_Cell |
PMC12479362 | Diseases with scarring risk were characterized by a uniquely high prevalence of F6: inflammatory myofibroblasts, which was not observed in low scarring risk or established fibrosis (Fig. 4b ). | [{'end': 111, 'label': 'CellType', 'start': 97, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | F7: myofibroblasts were observed at a similar prevalence in diseases with scarring risk and established fibrosis. | [{'end': 18, 'label': 'CellType', 'start': 4, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | These data point toward F6: inflammatory myofibroblast as a population influencing scarring risk, but which are largely absent in established fibrosis. | [{'end': 54, 'label': 'CellType', 'start': 41, 'text': 'myofibroblast'}] | Single_Cell |
PMC12479362 | F8: fascia-like myofibroblasts were also elevated in established fibrosis but were predominantly observed in Dupuytren contracture, a fibroproliferative disease of the palmar fascia (Fig. 4a ). | [{'end': 181, 'label': 'Tissue', 'start': 168, 'text': 'palmar fascia'}
{'end': 30, 'label': 'CellType', 'start': 16, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | We used two further approaches to demonstrate the role for distinct fibroblast subtypes predicting scarring risk. | [{'end': 78, 'label': 'CellType', 'start': 68, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | First, we trained a random forest classifier and identified that F6: inflammatory myofibroblasts and F7: myofibroblasts were the most important fibroblast subtypes for predicting scarring risk category (Extended Data Fig. 6b ). | [{'end': 119, 'label': 'CellType', 'start': 105, 'text': 'myofibroblasts'}
{'end': 96, 'label': 'CellType', 'start': 82, 'text': 'myofibroblasts'}
{'end': 154, 'label': 'CellType', 'start': 144, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | Second, we profiled a well-recognized myofibroblast marker (LRRC15) at the protein level. | [] | Single_Cell |
PMC12479362 | LRRC15 was evident in inflammation with scarring risk (inflamed hidradenitis suppurativa skin) but not in noninflamed skin or inflamed skin without scarring risk (atopic dermatitis skin) (Fig. 4c ). | [{'end': 93, 'label': 'Tissue', 'start': 89, 'text': 'skin'}
{'end': 122, 'label': 'Tissue', 'start': 118, 'text': 'skin'}
{'end': 139, 'label': 'Tissue', 'start': 135, 'text': 'skin'}
{'end': 185, 'label': 'Tissue', 'start': 181, 'text': 'skin'}] | Single_Cell |
PMC12479362 | Having established that disease-associated fibroblasts are enriched in distinct scarring categories, we next used spatial transcriptomics to validate these fibroblast populations in distinct scarring risk stroma (Fig. 4d–f and Supplementary Fig. 3 ) . | [{'end': 54, 'label': 'CellType', 'start': 43, 'text': 'fibroblasts'}
{'end': 166, 'label': 'CellType', 'start': 156, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | In keeping with scRNA-seq data (Fig. 4a ), F3: FRC-like fibroblasts were expanded in inflamed atopic dermatitis skin (low risk), without major myofibroblasts (Fig. 4d,f and Extended Data Fig. 6c ). | [{'end': 67, 'label': 'CellType', 'start': 47, 'text': 'FRC-like fibroblasts'}
{'end': 116, 'label': 'Tissue', 'start': 112, 'text': 'skin'}
{'end': 157, 'label': 'CellType', 'start': 143, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | We localized the F3: FRC-like population to the superficial perivascular immune niche (Fig. 4d ), which we further validated using 10x Visium data (Extended Data Fig. 6d–f ). | [{'end': 40, 'label': 'CellType', 'start': 21, 'text': 'FRC-like population'}
{'end': 85, 'label': 'Tissue', 'start': 73, 'text': 'immune niche'}] | Single_Cell |
PMC12479362 | In melanoma (scarring risk), aside from F1, the entire stroma comprised F6: inflammatory myofibroblasts and F7: myofibroblasts (Fig. 4e,f and Extended Data Fig. 6g ). | [{'end': 61, 'label': 'Tissue', 'start': 55, 'text': 'stroma'}
{'end': 126, 'label': 'CellType', 'start': 112, 'text': 'myofibroblasts'}
{'end': 103, 'label': 'CellType', 'start': 89, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | F7: myofibroblasts showed a matrix-producing phenotype ( COL1A1 , COL3A1 and POSTN ) that characterizes myofibroblastic cancer-associated fibroblasts (CAFs) (myoCAFs) . | [{'end': 18, 'label': 'CellType', 'start': 4, 'text': 'myofibroblasts'}
{'end': 149, 'label': 'CellType', 'start': 138, 'text': 'fibroblasts'}
{'end': 155, 'label': 'CellType', 'start': 151, 'text': 'CAFs'}
{'end': 165, 'label': 'CellType', 'start': 158, 'text': 'myoCAFs'}] | Single_Cell |
PMC12479362 | F6: inflammatory myofibroblasts demonstrated high expression of inflammatory CAF (iCAF) marker genes ( MMP1 , MMP3 , CXCL8 and IL24 ), which was observed in both cancer and inflammatory diseases with scarring risk (Extended Data Fig. 6h,i ). | [{'end': 31, 'label': 'CellType', 'start': 17, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | Finally, to complement our analysis of fibroblast proportions by disease, we assessed transcriptomic variability of disease-associated fibroblast subtypes by calculating gene module scores for each disease using defined marker genes to define transcriptomic variability across different disease conditions (Fig. 4g and M... | [{'end': 145, 'label': 'CellType', 'start': 135, 'text': 'fibroblast'}] | Single_Cell |
PMC12479362 | The F6: inflammatory myofibroblast signature score was highest in hidradenitis suppurativa, acne and keratinocytic skin cancers. | [] | Single_Cell |
PMC12479362 | Overall, our findings support distinct stromal composition in skin diseases associated with differential scarring risk. | [] | Single_Cell |
PMC12479362 | F6: inflammatory myofibroblasts were observed in diseases with scarring risk but relatively infrequently observed in established fibrosis, raising the possibility that they may be an intermediate differentiation state toward F7: myofibroblasts. | [{'end': 243, 'label': 'CellType', 'start': 229, 'text': 'myofibroblasts'}
{'end': 31, 'label': 'CellType', 'start': 17, 'text': 'myofibroblasts'}] | Single_Cell |
PMC12479362 | The differentiation process of healthy fibroblasts into myofibroblasts remains poorly understood in human tissues despite its clinical relevance. | [{'end': 70, 'label': 'CellType', 'start': 56, 'text': 'myofibroblasts'}
{'end': 50, 'label': 'CellType', 'start': 39, 'text': 'fibroblasts'}] | Single_Cell |
PMC12479362 | Fibroblasts are tissue resident, and thus intermediate states of myofibroblast differentiation are likely to be captured in the molecular snapshots of skin diseases analyzed. | [{'end': 11, 'label': 'CellType', 'start': 0, 'text': 'Fibroblasts'}] | Single_Cell |
PMC12479362 | We therefore performed trajectory analysis of fibroblasts in diseased skin to gain further insights into myofibroblast differentiation, before utilizing time-resolved human wound data as a validation of dynamic changes in stromal composition. | [{'end': 57, 'label': 'CellType', 'start': 46, 'text': 'fibroblasts'}
{'end': 74, 'label': 'Tissue', 'start': 70, 'text': 'skin'}] | Single_Cell |
PMC12479362 | We first included all fibroblast subtypes in a partition-based graph abstraction (PAGA) analysis (Extended Data Fig. 7a ), and then focused further analyses on fibroblast populations found across diseases on hair-bearing and hairless skin ( Methods ). | [{'end': 32, 'label': 'CellType', 'start': 22, 'text': 'fibroblast'}
{'end': 170, 'label': 'CellType', 'start': 160, 'text': 'fibroblast'}
{'end': 220, 'label': 'Tissue', 'start': 208, 'text': 'hair-bearing'}
{'end': 238, 'label': 'Tissue', 'start': 234, 'text': 'skin'}] | Single_Cell |
PMC12479362 | F7: myofibroblasts were a terminally differentiated myofibroblast state (Fig. 5a–c ), consistent with their presence in established fibrosis. | [{'end': 18, 'label': 'CellType', 'start': 4, 'text': 'myofibroblasts'}
{'end': 65, 'label': 'CellType', 'start': 52, 'text': 'myofibroblast'}] | Single_Cell |
PMC12479362 | We observed two potential sources for F7: myofibroblasts in skin across analyses (Fig. 5b,c and Extended Data Fig. 7b ). | [{'end': 56, 'label': 'CellType', 'start': 42, 'text': 'myofibroblasts'}
{'end': 64, 'label': 'Tissue', 'start': 60, 'text': 'skin'}] | Single_Cell |
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