关键词: ESC FGF8 IL17RD SEF iPSC isthmic organizer midbrain-hindbrain boundary organizer pluripotent stem cell

Mesh : Humans Animals Mice Homeodomain Proteins / metabolism Zebrafish / metabolism Fibroblast Growth Factor 8 / genetics Chickens / metabolism Mesencephalon / metabolism Pluripotent Stem Cells / metabolism Gene Expression Regulation, Developmental Fibroblast Growth Factors / metabolism Body Patterning

来  源:   DOI:10.1016/j.stemcr.2023.10.007   PDF(Pubmed)

Abstract:
In early vertebrate development, organizer regions-groups of cells that signal to and thereby influence neighboring cells by secreted morphogens-play pivotal roles in the establishment and maintenance of cell identities within defined tissue territories. The midbrain-hindbrain organizer drives regionalization of neural tissue into midbrain and hindbrain territories with fibroblast growth factor 8 (FGF8) acting as a key morphogen. This organizer has been extensively studied in chicken, mouse, and zebrafish. Here, we demonstrate the enrichment of FGF8-expressing cells from human pluripotent stem cells (hPSCs), cultured as attached embryoid bodies using antibodies that recognize \"Similar Expression to Fgf\" (SEF) and Frizzled proteins. The arrangement of cells in embryoid body subsets of these cultures and the gene expression profile of the FGF8-expressing population show certain similarities to the midbrain-hindbrain organizer in animal models. In the embryonic chick brain, the enriched cell population induces formation of midbrain structures, consistent with FGF8-organizing capability.
摘要:
在早期脊椎动物发育中,组织者区域-通过分泌的形态发生素向相邻细胞发出信号并由此影响相邻细胞的细胞群-在确定的组织区域内细胞身份的建立和维持中起关键作用。中脑-后脑组织者将神经组织区域化为中脑和后脑区域,成纤维细胞生长因子8(FGF8)作为关键形态发生原。这个组织者已经在鸡肉中进行了广泛的研究,鼠标,还有斑马鱼.这里,我们证明了从人类多能干细胞(hPSC)中富集表达FGF8的细胞,使用识别“与Fgf相似表达”(SEF)和Frizzled蛋白的抗体作为附着的胚状体进行培养。这些培养物的胚状体亚群中的细胞排列以及FGF8表达群体的基因表达谱显示出与动物模型中的中脑-后脑组织者的某些相似性。在胚胎小鸡的大脑中,富集的细胞群诱导中脑结构的形成,与FGF8组织能力一致。
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