Distinct molecular profile and restricted stem cell potential defines the prospective human cranial neural crest from embryonic stem cell state.
Distinct molecular profile and restricted stem cell potential defines the prospective human cranial neural crest from embryonic stem cell state.
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DOI：
10.1016/j.scr.2020.102086
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发表时间：
2020-12
影响因子：
1.2
通讯作者：
García-Castro MI
中科院分区：
文献类型：
--
作者：
Prasad MS;Charney RM;Patel LJ;García-Castro MI
神经嵴细胞是胚胎多能干细胞群。最近对模型生物体的研究表明，神经嵴细胞在囊胚阶段比之前想象的更早被指定。然而，早期神经嵴规范的分子动力学以及从多能前体到早期特定 NC 的功能变化仍有待阐明。在本报告中，我们利用强大的人类颅神经嵴形成模型来解决神经嵴规范最早阶段的独特分子特征，并评估其与其胚胎干细胞前体的功能差异。我们的人类神经嵴模型揭示了神经嵴和多能性基因的表观遗传状态的快速变化，伴随着胚胎干细胞基于 Wnt 的诱导后基因表达的变化。这些基因表达的变化直接受到β-连环蛋白转录活性的调节。此外，与胚胎干细胞相比，前瞻性颅神经嵴细胞的干细胞潜力有限。我们的结果表明，由人胚胎干细胞的 Wnt/β-连环蛋白信号传导诱导的人神经嵴快速获得由独特的分子特征定义的预期神经嵴细胞状态，并且与多能干细胞相比，其潜力有限。
Neural crest cells are an embryonic multipotent stem cell population. Recent studies in model organisms have suggested that neural crest cells are specified earlier than previously thought, at blastula stages. However, the molecular dynamics of early neural crest specification, and functional changes from pluripotent precursors to early specified NC, remain to be elucidated. In this report, we utilized a robust human model of cranial neural crest formation to address the distinct molecular character of the earliest stages of neural crest specification and assess the functional differences from its embryonic stem cell precursor. Our human neural crest model reveals a rapid change in the epigenetic state of neural crest and pluripotency genes, accompanied by changes in gene expression upon Wnt-based induction from embryonic stem cells. These changes in gene expression are directly regulated by the transcriptional activity of β-catenin. Furthermore, prospective cranial neural crest cells are characterized by restricted stem cell potential compared to embryonic stem cells. Our results suggest that human neural crest induced by Wnt/β-catenin signaling from human embryonic stem cells rapidly acquire a prospective neural crest cell state defined by a unique molecular signature and endowed with limited potential compared to pluripotent stem cells.
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影响因子：
3.7
作者：
Fukuta M;Nakai Y;Kirino K;Nakagawa M;Sekiguchi K;Nagata S;Matsumoto Y;Yamamoto T;Umeda K;Heike T;Okumura N;Koizumi N;Sato T;Nakahata T;Saito M;Otsuka T;Kinoshita S;Ueno M;Ikeya M;Toguchida J
通讯作者：
Toguchida J
影响因子：
4.6
作者：
Gomez, Gustavo A.;Prasad, Maneeshi S.;Garcia-Castro, Martin I.
通讯作者：
Garcia-Castro, Martin I.
DOI：
10.1002/bdrc.20013
发表时间：
2004-06-01
期刊：
Birth defects research. Part C, Embryo today : reviews
影响因子：
--
作者：
Farlie, Peter G;McKeown, Sonja J;Newgreen, Donald F
通讯作者：
Newgreen, Donald F
影响因子：
64.8
作者：
Basch, ML;Bronner-Fraser, M;García-Castro, MI
通讯作者：
García-Castro, MI
影响因子：
23.9
作者：
Carey, Bryce W.;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf