A prenatal skin atlas reveals immune regulation of human skin morphogenesis
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 skin<sup>1</sup>. 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.
Authors
- Steven Lisgo (ORCID: https://orcid.org/0000-0001-5186-3971)
- Antony Rose (ORCID: https://orcid.org/0000-0001-8494-8138)
- Elizabeth Poyner (ORCID: https://orcid.org/0000-0002-0443-9980)
- Pavel Mazin (ORCID: https://orcid.org/0000-0001-9268-3352)
- Omer Ali Bayraktar (ORCID: https://orcid.org/0000-0001-6055-277X)
- Anna Dubois (ORCID: https://orcid.org/0000-0002-5248-3687)
- Roser Vento‐Tormo (ORCID: https://orcid.org/0000-0002-9870-8474)
- Vijaya Baskar Mahalingam Shanmugiah
- Fereshteh Torabi (ORCID: https://orcid.org/0009-0008-8660-3350)
- Laure Gambardella (ORCID: https://orcid.org/0000-0001-5771-1565)
- Dorin-Mirel Popescu
- Catherine Tudor (ORCID: https://orcid.org/0000-0003-2093-9683)
- Dinithi Sumanaweera (ORCID: https://orcid.org/0000-0003-4515-0988)
- Justin Englebert
- Andrew Filby (ORCID: https://orcid.org/0000-0001-9078-4360)
- John E. Lawrence (ORCID: https://orcid.org/0000-0002-7951-915X)
- Sara A. Serdy (ORCID: https://orcid.org/0000-0002-6076-9749)
- Barbara Treutlein (ORCID: https://orcid.org/0000-0002-3299-5597)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- Kwasi Kwakwa
- Gary Reynolds (ORCID: https://orcid.org/0000-0002-8142-8708)
- Stéphane Ballereau (ORCID: https://orcid.org/0000-0002-8479-3110)
- Nusayhah Hudaa Gopee (ORCID: https://orcid.org/0000-0001-8507-5682)
- Sophie Pritchard (ORCID: https://orcid.org/0000-0001-5580-4848)
- Jiyoon Lee (ORCID: https://orcid.org/0000-0002-5561-5331)
- Emily Stephenson (ORCID: https://orcid.org/0000-0002-4244-4019)
- Maria Kasper (ORCID: https://orcid.org/0000-0002-6117-2717)
- Fränze Progatzky (ORCID: https://orcid.org/0000-0003-0784-1323)
- Tong Li
- Kenny S. Roberts (ORCID: https://orcid.org/0000-0001-6155-0821)
- Chloe Admane (ORCID: https://orcid.org/0009-0005-9327-9008)
- Mohi Miah (ORCID: https://orcid.org/0000-0001-5617-5350)
- Rachel A. Botting (ORCID: https://orcid.org/0000-0001-9595-4605)
- Issac Goh (ORCID: https://orcid.org/0000-0002-6397-3518)
- Elena Winheim (ORCID: https://orcid.org/0000-0002-0364-662X)
- Anh Phuong Le (ORCID: https://orcid.org/0000-0002-0477-9969)
- Neil Rajan (ORCID: https://orcid.org/0000-0002-5850-5680)
- Muzlifah A. Haniffa (ORCID: https://orcid.org/0000-0002-3927-2084)
- Diana Adão (ORCID: https://orcid.org/0000-0002-6678-4923)
- Alyson Guy (ORCID: https://orcid.org/0000-0002-1199-5395)
- James Fletcher (ORCID: https://orcid.org/0000-0001-9610-1858)
- Lloyd Steele (ORCID: https://orcid.org/0000-0003-4745-1338)
- Pejvak Moghimi
- Laura Jardine (ORCID: https://orcid.org/0000-0003-4495-8205)
- Win Tun (ORCID: https://orcid.org/0000-0003-0991-8785)
- Ian A. Glass (ORCID: https://orcid.org/0000-0001-6762-8407)
- Ni Huang (ORCID: https://orcid.org/0000-0001-8849-038X)
- Keval Sidhpura (ORCID: https://orcid.org/0009-0007-4077-7120)
- Marina Nikolova (ORCID: https://orcid.org/0000-0002-8212-049X)
- Roger A. Barker (ORCID: https://orcid.org/0000-0001-8843-7730)
- Bayanne Olabi (ORCID: https://orcid.org/0000-0002-4786-7838)
- Clarisse Gânier
- Karl R. Koehler (ORCID: https://orcid.org/0000-0002-0685-538X)
- CiCi Deakin
- Karl Annusver (ORCID: https://orcid.org/0000-0002-9515-7216)
- Edel A. O’Toole (ORCID: https://orcid.org/0000-0002-4084-4836)
- Dave Horsfall (ORCID: https://orcid.org/0000-0002-8086-812X)
- Nana-Jane Chipampe (ORCID: https://orcid.org/0000-0002-8802-0473)
- April Foster (ORCID: https://orcid.org/0000-0002-5397-4365)
- Josh Moore (ORCID: https://orcid.org/0000-0003-4028-811X)
- John A. McGrath (ORCID: https://orcid.org/0000-0002-3708-9964)
- Ilaria Mulas (ORCID: https://orcid.org/0000-0003-2556-9685)
- Kelly Y Gim (ORCID: https://orcid.org/0009-0003-5634-6836)
- Ben Rumney
- Daniela Basurto Lozada
- Jin Kim (ORCID: https://orcid.org/0000-0002-7667-9588)
- Peng He (ORCID: https://orcid.org/0000-0002-2457-3554)
- Jong-Eun Park (ORCID: https://orcid.org/0000-0002-1687-2423)
- Claire Hale (ORCID: https://orcid.org/0009-0000-8265-1082)
- Vicky Rowe
- Luca Verger (ORCID: https://orcid.org/0009-0007-9108-4711)
Institutions
- Boston Children's Hospital (US)
- Guy's Hospital (GB)
- Queen Mary University of London (GB)
- University of California, San Francisco (US)
- King's College London (GB)
- University of Washington (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Wellcome Sanger Institute (GB)
- Karolinska Institutet (SE)
- ETH Zurich (CH)
- University of Oxford (GB)
- NIHR Newcastle Biomedical Research Centre (GB)
- Boston Children's Museum (US)
- German BioImaging – Gesellschaft für Mikroskopie und Bildanalyse
- Newcastle University (GB)
Publication Details
- Journal
- Nature
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41586-024-08002-x
- Citations
- 81
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 18.71
Funders
- Medical Research Council