at baseline, myof ibroblasts were not present, but on day 1 post - wounding, a small number of f6: inflammatory myof ibroblasts were observed ( fig. 5d and extended data fig. 7c ). by day 7, f6: inflammatory myof ibroblasts were the predominant population. by day 30, f7: myof ibroblasts had become the predominant population, consistent with a role in established fibrosis / scarring. overall, our results point toward f6: inflammatory myof ibroblasts as an intermediate differentiation state toward f7: myof ibroblasts in human skin, with potential plasticity in fibroblast origin ( fig. 5d, e and extended data fig. 7e ). we next investigated if the skin fibroblast subtypes we identified were conserved across other human tissues. previous studies have reported fibroblast states that are found across human tissues. however, because these studies each defined fibroblast subtypes with different nomenclature and gene markers, it is unclear how these populations relate to each other and to the skin fibroblast populations reported in our study. to answer this and perform an overarching analysis across tissues and diseases, we undertook two approaches. the first was to assess the expression of marker genes for cross - tissue fibroblast subtypes in our skin data. this identified that reported cross - tissue populations from previous studies are likely present in human skin, consistent with f2: universal, f3: frc - like, f6: inflammatory myof ibroblast, and f7: myof ibroblast subtypes ( fig. 6a and extended data fig. 8a ). the second approach was to integrate published datasets of ~ 5. 8 million cells from human skin, lung, intestine, synovium, endometrium, heart and nasal mucosa ( methods and fig. 6b ). this approach uses the whole transcriptome profile, instead of restricted marker genes, and thus more comprehensively defines cell state similarity. approximately 1 million fibroblasts were selected for downstream analysis based on expression of canonical marker genes ( fig. 6b ). in the cross - tissue integrated dataset, we were able to discern shared fibroblast states across tissues, as well as fibroblasts that were unique to certain tissues ( fig. 6b, c and extended data fig. 8b ). in addition to known cross - tissue populations identified above ( fig. 6a ), we found evidence for f2 / 3: perivascular ( cxcl12, apoc1 and pparg ) and f5: ngfr ( schwann - like; scn7a, ngfr, itga6 and ebf2 ) fibroblasts across human tissues, including in lung, gut and nasal mucosa ( fig. 6c, d and extended data fig. 8b, c ). further interrogation of labeled intestine and lung datasets supported these results ( supplementary note 3 ). f1: superficial showed variable gene expression by tissue, which may reflect distinc t epithelia patterning across sites ( extended data fig. 8d ). overall, our results point toward the presence of previously reported cross - tissue fibroblast states in skin, despite major differences in the biophysical properties of different human tissues. we additionally suggest f2 / 3: perivascular and f5: ngfr ( nerve - associated ) fibroblasts as novel cross - tissue populations. fibroblast - mediated processes such as fibrosis and maintenance of immune cell niches are observed across multiple human tissues. we therefore asked whether disease-associated fibroblast states identified in skin were similarly enriched by disease category in non - skin tissues ( methods ). we focused on f3: frc - like and f6: inflammatory myof ibroblasts based on their conserved states across tissues and potential immune - interacting roles from pathway enrichment analysis ( extended data figs. 2a and 5c ). then, to predict functional interactions with immune cells, we utilized our skin data to perform cell – cell communication analysis. across tissues, we observed that f3: frc - like fibroblasts were present in both inflammatory disor ders and fibrotic processes with immune-mediated pathology, including lung ( covid - 19 and interstitial lung disease ) and intestine ( inflammatory bowel disease ( ibd ) ) ( fig. 7a, b ). while frc - like fibroblasts were not reported in the human lung cell atlas ( hlca ), following re - clustering we identified an f3: frc - like population in lung ( extended data fig. 8e, f ), consistent with a previous report. we also confirmed equivalence of f3: frc - like fibroblasts to t reticular cells ( an frc subset ) in ibd ( supplementary note 3 and extended data fig. 8g ). receptor – ligand analysis suggested interactions of skin f3: frc - like fibroblasts with migrating dendritic cells ( migdcs ) ( ccl19 - ccr7 ) and t cell subsets ( cxcl12 - cxcr4 ) ( extended data fig. 9a ), suggesting that f3: frc - like fibroblasts maintain t lymphoid populations and facilitate t cell – dendritic cell interactions analogous to t reticular cells in lymphoid tissue. we corroborated these findings using nichecompass for niche identification in inflamed atopic dermatitis skin, which revealed ccr7 migdcs and cxcr4 t cells within the f3 superficial perivascular niche ( fig. 7c and extended data fig. 9b ). f6: inflammatory myof ibroblasts were abundant in cancer and inflammation but relatively uncommon in established fibrosis ( fig. 7a, b ), consistent with skin data ( fig. 4b ). inflammatory myof ibroblasts are well described in ibd, and we confirmed equivalence of these cells to skin f6: inflammatory myof ibroblasts ( supplementary note 3 and extended data fig. 8g ). to further assess the clinical relevance of f6 in ibd, we used an scrna - seq dataset with clinical metadata. f6: inflammatory myof ibroblasts were significantly elevated in inflamed tissue, compared to non - inflamed tissue, and their prevalence correlated with clinical inflammation severity scores ( fig. 7e ). receptor – ligand analysis suggested that f6: inflammatory myof ibroblasts recruit and maintain neutrophils ( cxcl5 / 6 / 8 - cxcr2 and csf3 - csf3r ), macrophages / monocytes ( ccl5 / 26 - ccr1 and csf3 - csf3r ) and b cells ( cxcl13 / cxcr5 ) in the skin ( fig. 7c and methods ). these genes were highly expressed in the skin during wound healing, acne and hidradenitis suppurativa, as well as in ibd and lung cancer ( fig. 7b ), suggesting a similar mechanism for recruitment of immune cells across tissues. overall, our results suggest that f3: frc - like ( ccl19 cd74 tnfrsf13b and il33 / il15 ) and f6: inflammatory myof ibroblasts ( il11 mmp1 cxcl5 il7r ) mediate distinc t immune niches driving pathology in the skin and other tissues ( fig. 7f ). given the similar transcriptomic profiles of adult skin f3: frc - like and intestinal t reticular cells, we hypothesized that these fibroblasts had similar origins in their respective tissues. intestinal frcs are found in the peyer ’ s patch and are thought to arise from prenatal lymphoid tissue organizer ( lto ) cells; however, the skin does not harbor the equivalent of peyer ’ s patch and the origin of f3: frc - like cells remains unknown. to explore f3 ontogeny from a developmental perspective, we first integrated adult and prenatal skin fibroblasts and identified the corresponding fibroblast populations ( supplementary note 4 ). this identified that adult f3: frc - like fibroblasts correlated with prenatal skin ccl19 fibroblasts ( fig. 8a, b ). we next queried whether prenatal ccl19 fibroblasts were equivalent to lto - like cells by jointly integrating human prenatal skin and intestinal data. notably, prenatal skin ccl19 cells and prenatal intestinal mesenchymal lto cells clustered together ( fig. 8c ). prenatal skin ccl19 cells expressed known mesenchymal lto markers, including ccl21, cxcl13, madcam1, fdcsp and tnfsf11 ( rankl ) ( fig. 8c ), suggesting that prenatal skin ccl19 cells may give rise to adult skin f3: frc - like cells in a manner analogous to intestinal lto cells. we next investigated the lto gene program in adult skin f3: frc - like fibroblasts.