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Here, we compared small non-regenerative and large regenerative skin wounds to investigate how fibroblasts acquire regenerative competence and enter alternative cell-fate programs. Integrated single-cell RNA sequencing identified a transient signaling and extracellular-matrix-remodeling niche enriched in large wounds, together with NCAM1-associated competent fibroblast states. Time-resolved analysis positioned these states within a root-like fibroblast manifold connected to hair dermal-condensate, endothelial, pericyte and glial-associated fate-entry programs. Inferred cell-cell communication networks revealed shared matrix and adhesion signals, superimposed with branch-associated inputs, including VEGF signaling toward NCAM1-positive endothelial-transition cells. Lineage tracing showed that PDGFRA- and NCAM1-expressing lineages contributed to vascular- and nerve\/glial-associated regenerative compartments. Functionally, partial NCAM1 perturbation reduced vascular organization while increasing hair follicle neogenesis, whereas stronger inhibition impaired both outcomes. These findings identify NCAM1 as a regulator of regenerative competence and fate specification within a regenerative competence field rather than a marker of a single terminal lineage. We propose that regenerative wounds activate an NCAM1-associated fibroblast competence field whose quantitative modulation biases competent fibroblasts toward alternative outcomes.<\/jats:p>","DOI":"10.64898\/2026.10.01.756129","type":"posted-content","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:00:12Z","timestamp":1791190812000},"source":"Crossref","is-referenced-by-count":0,"title":["A regenerative fibroblast competence field supports multiple cell fates in adult skin regeneration"],"prefix":"10.64898","author":[{"given":"Chih-Han","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"},{"name":"Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Kuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen Yuan","family":"Kam","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095"},{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095"},{"name":"Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Van Handel","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arijita","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chun","family":"Ho","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Evseenko","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"},{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ming","family":"Chuong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans I-Chen","family":"Harn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100808500584000_2026.10.01.756129v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.07.008"},{"key":"2026100808500584000_2026.10.01.756129v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3904"},{"key":"2026100808500584000_2026.10.01.756129v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"2026100808500584000_2026.10.01.756129v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.016"},{"key":"2026100808500584000_2026.10.01.756129v1.5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jare.2025.09.040","article-title":"Roles of Msx2 in exogen control: modulating the stem cell niche during the transition from hair shedding to regeneration","volume":"84","year":"2026","journal-title":"J Adv Res"},{"key":"2026100808500584000_2026.10.01.756129v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21551"},{"key":"2026100808500584000_2026.10.01.756129v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature12783"},{"key":"2026100808500584000_2026.10.01.756129v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature10137"},{"key":"2026100808500584000_2026.10.01.756129v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.044"},{"key":"2026100808500584000_2026.10.01.756129v1.10","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-8-376"},{"key":"2026100808500584000_2026.10.01.756129v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3181"},{"key":"2026100808500584000_2026.10.01.756129v1.12","doi-asserted-by":"crossref","unstructured":"Gerber, T. , P. 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