TY - JOUR
KW - Angiogenesis
KW - Computational biology and bioinformatics
KW - induced pluripotent stem cells
KW - Microglial cells
KW - Morphogenesis
AU - Nusayhah Hudaa Gopee
AU - Elena Winheim
AU - Bayanne Olabi
AU - Chloe Admane
AU - April Rose Foster
AU - Ni Huang
AU - Rachel A. Botting
AU - Fereshteh Torabi
AU - Dinithi Sumanaweera
AU - Anh Phuong Le
AU - Jin Kim
AU - Luca Verger
AU - Emily Stephenson
AU - Diana Adão
AU - Clarisse Ganier
AU - Kelly Y. Gim
AU - Sara A. Serdy
AU - CiCi Deakin
AU - Issac Goh
AU - Lloyd Steele
AU - Karl Annusver
AU - Mohi-Uddin Miah
AU - Win Min Tun
AU - Pejvak Moghimi
AU - Kwasi Amoako Kwakwa
AU - Tong Li
AU - Daniela Basurto Lozada
AU - Ben Rumney
AU - Catherine L. Tudor
AU - Kenny Roberts
AU - Nana-Jane Chipampe
AU - Keval Sidhpura
AU - Justin Englebert
AU - Laura Jardine
AU - Gary Reynolds
AU - Antony Rose
AU - Vicky Rowe
AU - Sophie Pritchard
AU - Ilaria Mulas
AU - James Fletcher
AU - Dorin-Mirel Popescu
AU - Elizabeth Poyner
AU - Anna Dubois
AU - Alyson Guy
AU - Andrew Filby
AU - Steven Lisgo
AU - Roger A. Barker
AU - Ian A. Glass
AU - Jong-Eun Park
AU - Roser Vento-Tormo
AU - Marina Tsvetomilova Nikolova
AU - Peng He
AU - John E. G. Lawrence
AU - Josh Moore
AU - Stephane Ballereau
AU - Christine B. Hale
AU - Vijaya Shanmugiah
AU - David Horsfall
AU - Neil Rajan
AU - John A. McGrath
AU - Edel A. O’Toole
AU - Barbara Treutlein
AU - Omer Bayraktar
AU - Maria Kasper
AU - Fränze Progatzky
AU - Pavel Mazin
AU - Jiyoon Lee
AU - Laure Gambardella
AU - Karl R. Koehler
AU - Sarah A. Teichmann
AU - Muzlifah Haniffa
AB - Human 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.
BT - Nature
DA - 2024-11
DO - 10.1038/s41586-024-08002-x
IS - 8039
LA - en
N2 - Human 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.
PY - 2024
SP - 679
EP - 689
T2 - Nature
TI - A prenatal skin atlas reveals immune regulation of human skin morphogenesis
UR - https://www.nature.com/articles/s41586-024-08002-x
VL - 635
Y2 - 2024-11-26
SN - 1476-4687
ER -