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Summary Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation towards cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis.

Introduction The development of reporting guidelines over the past 20 years represents a major advance in scholarly publishing with recent evidence showing positive impacts. Whilst over 350 reporting guidelines exist, there are few that are specific to surgery. Here we describe the development of the STROCSS guideline (Strengthening the Reporting of Cohort Studies in Surgery). Methods and analysis We published our protocol apriori. Current guidelines for case series (PROCESS), cohort studies (STROBE) and randomised controlled trials (CONSORT) were analysed to compile a list of items which were used as baseline material for developing a suitable checklist for surgical cohort guidelines. These were then put forward in a Delphi consensus exercise to an expert panel of 74 surgeons and academics via Google Forms. Results The Delphi exercise was completed by 62% (46/74) of the participants. All the items were passed in a single round to create a STROCSS guideline consisting of 17 items. Conclusion We present the STROCSS guideline for surgical cohort, cross-sectional and case-control studies consisting of a 17-item checklist. We hope its use will increase the transparency and reporting quality of such studies. This guideline is also suitable for cross-sectional and case control studies. We encourage authors, reviewers, journal editors and publishers to adopt these guidelines.

Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage–positive fibroblasts (EPFs) are known to function in scarring, but Engrailed-1 lineage–negative fibroblasts (ENFs) remain poorly characterized. Using cell transplantation and transgenic mouse models, we identified a dermal ENF subpopulation that gives rise to postnatally derived EPFs by activating Engrailed-1 expression during adult wound healing. By studying ENF responses to substrate mechanics, we found that mechanical tension drives Engrailed-1 activation via canonical mechanotransduction signaling. Finally, we showed that blocking mechanotransduction signaling with either verteporfin, an inhibitor of Yes-associated protein (YAP), or fibroblast-specific transgenic YAP knockout prevents Engrailed-1 activation and promotes wound regeneration by ENFs, with recovery of skin appendages, ultrastructure, and mechanical strength. This finding suggests that there are two possible outcomes to postnatal wound healing: a fibrotic response (EPF-mediated) and a regenerative response (ENF-mediated).

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