英国纽卡斯尔大学Muzlifah Haniffa等研究人员合作研究团队发现，一个胎儿皮肤图谱揭示免疫调控在人类皮肤形态发生中的作用。该项研究成果于2024年10月16日在线发表在《自然》杂志上。

研究人员通过结合单细胞和空间转录组数据，构建了一个全面的人类胎儿皮肤多组学参考图谱（7至17受孕周），以表征皮肤的微解剖组织环境。该图谱揭示了非免疫细胞与免疫细胞之间的交流对于毛囊的形成、无疤痕愈合以及皮肤血管生成至关重要。

研究人员系统性地将一个来源于人类胚胎干细胞和诱导多能干细胞的毛发生长皮肤类器官（SkO）模型与胎儿和成年皮肤进行比较。SkO模型在毛囊发育过程中，真实再现了体内皮肤表皮和真皮细胞类型，并表达了与遗传性毛发和皮肤疾病发病机制相关的基因。然而，SkO模型中缺乏免疫细胞，且内皮细胞的异质性和数量明显减少。

该体内胎儿皮肤细胞图谱显示，巨噬细胞及其分泌的生长因子在驱动内皮发育中发挥作用。事实上，当将来源于诱导多能干细胞的自体巨噬细胞转移到SkO培养物中后，血管网络的重塑得到了增强。因此，固有免疫细胞不仅在免疫中发挥传统作用，还通过与非免疫细胞的交流，在皮肤形态发生中起到了关键作用。

研究人员表示，人类的胎儿皮肤中存在固有免疫细胞，包括巨噬细胞，但它们是否仅在免疫中发挥作用或在形态发生中有额外功能尚不明确。

附：英文原文

Title: A prenatal skin atlas reveals immune regulation of human skin morphogenesis

Author: Gopee, Nusayhah Hudaa, Winheim, Elena, Olabi, Bayanne, Admane, Chloe, Foster, April Rose, Huang, Ni, Botting, Rachel A., Torabi, Fereshteh, Sumanaweera, Dinithi, Le, Anh Phuong, Kim, Jin, Verger, Luca, Stephenson, Emily, Ado, Diana, Ganier, Clarisse, Gim, Kelly Y., Serdy, Sara A., Deakin, CiCi, Goh, Issac, Steele, Lloyd, Annusver, Karl, Miah, Mohi-Uddin, Tun, Win Min, Moghimi, Pejvak, Kwakwa, Kwasi Amoako, Li, Tong, Basurto Lozada, Daniela, Rumney, Ben, Tudor, Catherine L., Roberts, Kenny, Chipampe, Nana-Jane, Sidhpura, Keval, Englebert, Justin, Jardine, Laura, Reynolds, Gary, Rose, Antony, Rowe, Vicky, Pritchard, Sophie, Mulas, Ilaria, Fletcher, James, Popescu, Dorin-Mirel, Poyner, Elizabeth, Dubois, Anna, Guy, Alyson, Filby, Andrew, Lisgo, Steven, Barker, Roger A., Glass, Ian A., Park, Jong-Eun, Vento-Tormo, Roser, Nikolova, Marina Tsvetomilova, He, Peng, Lawrence, John E. G., Moore, Josh, Ballereau, Stephane, Hale, Christine B., Shanmugiah, Vijaya, Horsfall, David, Rajan, Neil, McGrath, John A., OToole, Edel A., Treutlein, Barbara, Bayraktar, Omer, Kasper, Maria, Progatzky, Frnze

Issue&Volume: 2024-10-16

Abstract: 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 (7–17post-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.

DOI: 10.1038/s41586-024-08002-x

Source: https://www.nature.com/articles/s41586-024-08002-x