04361nas a2201057   4500000000100000000000100001008004100002260001200043653001700055653004500072653003500117653002100152653001800173100002500191700001800216700001800234700001700252700002200269700001300291700002200304700002100326700002400347700001800371700001200389700001600401700002100417700001600438700002000454700001700474700001800491700001600509700001400525700001700539700001800556700002000574700001600594700001900610700002400629700001200653700002700665700001500692700002300707700001800730700002300748700001900771700002100790700001800811700001800829700001600847700001500863700002100878700001700899700001900916700002400935700002100959700001600980700001500996700001701011700001701028700002001045700001701065700001801082700002201100700003301122700001201155700002401167700001501191700002301206700002201229700002201251700001901273700001501292700002001307700002201327700002201349700001901371700001701390700002201407700001601429700001501445700002201460700002001482700002301502700002101525245008001546856005501626300001201681490000801693520158801701022001403289       2024                            d  c2024-1110aAngiogenesis10aComputational biology and bioinformatics10ainduced pluripotent stem cells10aMicroglial cells10aMorphogenesis1 aNusayhah Hudaa Gopee1 aElena Winheim1 aBayanne Olabi1 aChloe Admane1 aApril Rose Foster1 aNi Huang1 aRachel A. Botting1 aFereshteh Torabi1 aDinithi Sumanaweera1 aAnh Phuong Le1 aJin Kim1 aLuca Verger1 aEmily Stephenson1 aDiana Adão1 aClarisse Ganier1 aKelly Y. Gim1 aSara A. Serdy1 aCiCi Deakin1 aIssac Goh1 aLloyd Steele1 aKarl Annusver1 aMohi-Uddin Miah1 aWin Min Tun1 aPejvak Moghimi1 aKwasi Amoako Kwakwa1 aTong Li1 aDaniela Basurto Lozada1 aBen Rumney1 aCatherine L. Tudor1 aKenny Roberts1 aNana-Jane Chipampe1 aKeval Sidhpura1 aJustin Englebert1 aLaura Jardine1 aGary Reynolds1 aAntony Rose1 aVicky Rowe1 aSophie Pritchard1 aIlaria Mulas1 aJames Fletcher1 aDorin-Mirel Popescu1 aElizabeth Poyner1 aAnna Dubois1 aAlyson Guy1 aAndrew Filby1 aSteven Lisgo1 aRoger A. Barker1 aIan A. Glass1 aJong-Eun Park1 aRoser Vento-Tormo1 aMarina Tsvetomilova Nikolova1 aPeng He1 aJohn E. G. Lawrence1 aJosh Moore1 aStephane Ballereau1 aChristine B. Hale1 aVijaya Shanmugiah1 aDavid Horsfall1 aNeil Rajan1 aJohn A. McGrath1 aEdel A. O’Toole1 aBarbara Treutlein1 aOmer Bayraktar1 aMaria Kasper1 aFränze Progatzky1 aPavel Mazin1 aJiyoon Lee1 aLaure Gambardella1 aKarl R. Koehler1 aSarah A. Teichmann1 aMuzlifah Haniffa00aA prenatal skin atlas reveals immune regulation of human skin morphogenesis  uhttps://www.nature.com/articles/s41586-024-08002-x  a679-6890 v6353 aHuman prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7–17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.  a1476-4687