Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Molecular Pathophysiology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan.
Dev Dyn. 2024 Jan;253(1):59-77. doi: 10.1002/dvdy.532. Epub 2022 Sep 13.
The somatopleure serves as the primordium of the amnion, an extraembryonic membrane surrounding the embryo. Recently, we have reported that amniogenic somatopleural cells (ASCs) not only form the amnion but also migrate into the embryo and differentiate into cardiomyocytes and vascular endothelial cells. However, detailed differentiation processes and final distributions of these intra-embryonic ASCs (hereafter referred to as iASCs) remain largely unknown.
By quail-chick chimera analysis, we here show that iASCs differentiate into various cell types including cardiomyocytes, smooth muscle cells, cardiac interstitial cells, and vascular endothelial cells. In the pharyngeal region, they distribute selectively into the thyroid gland and differentiate into vascular endothelial cells to form intra-thyroid vasculature. Explant culture experiments indicated sequential requirement of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling for endothelial differentiation of iASCs. Single-cell transcriptome analysis further revealed heterogeneity and the presence of hemangioblast-like cell population within ASCs, with a switch from FGF to VEGF receptor gene expression.
The present study demonstrates novel roles of ASCss especially in heart and thyroid development. It will provide a novel clue for understanding the cardiovascular development of amniotes from embryological and evolutionary perspectives.
体壁层作为胎膜的原基，围绕胚胎的一种胚外膜。最近，我们报道了胚外体壁层细胞（ASCs）不仅形成胎膜，还迁移到胚胎中并分化为心肌细胞和血管内皮细胞。然而，这些胚胎内 ASC（以下简称 iASC）的详细分化过程和最终分布仍知之甚少。
通过鹌鹑-鸡嵌合体分析，我们发现 iASC 可分化为多种细胞类型，包括心肌细胞、平滑肌细胞、心脏间质细胞和血管内皮细胞。在咽区，它们选择性地分布到甲状腺中，并分化为血管内皮细胞，形成甲状腺内血管。外植体培养实验表明，iASC 的内皮分化需要依次激活成纤维细胞生长因子（FGF）和血管内皮生长因子（VEGF）信号通路。单细胞转录组分析进一步揭示了 ASC 中的异质性和存在类血岛细胞群体，其 FGF 受体基因表达向 VEGF 受体基因表达转变。
本研究揭示了 ASC 的新功能，特别是在心脏和甲状腺发育中的作用。它将为从胚胎学和进化角度理解羊膜动物心血管发育提供新的线索。
