NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl.

NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl.
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DOI:
10.1371/journal.pbio.3002121
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发表时间:
2023-06
期刊:
影响因子:
9.8
通讯作者:
--
中科院分区:
生物学1区
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多能性定义了脊椎动物胚胎单个细胞的无限潜力,所有成年体细胞和生殖细胞都来自于脊椎动物胚胎。由于缺乏来自低等脊椎动物的数据,人们在一定程度上无法理解多能性基因的进化过程;在青蛙和斑马鱼等模式系统中,多能性基因NANOG和Pou5f1的功能存在分歧。在这里,我们调查了NANOG的Axolotl同源基因是如何在发育过程中实现多能性的。紫杉醇NANOG对于原肠形成和胚层承诺是绝对必要的。我们发现,在Axolotl原始外胚层(动物CAPS;ACS)中,NANOG和节点活性以及表观遗传修饰酶DPY30是H3K4me3在多能染色质中大量沉积所必需的。我们还证明,所有3种蛋白质活性都是急性冠脉综合征建立分化为中胚层的能力所必需的。我们的结果提示,NANOG的古老功能可能是在早期细胞中建立谱系分化的能力。这些观察为陆地脊椎动物进化而来的四足动物祖先的胚胎发育提供了洞察力。Nanog和Nodal在建立两栖类(Axolotl)多能性中的作用表明,支持多能性的基因调控网络是保守的,并为中胚层的进化提供了基础。
Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development. Axolotl NANOG is absolutely required for gastrulation and germ-layer commitment. We show that in axolotl primitive ectoderm (animal caps; ACs) NANOG and NODAL activity, as well as the epigenetic modifying enzyme DPY30, are required for the mass deposition of H3K4me3 in pluripotent chromatin. We also demonstrate that all 3 protein activities are required for ACs to establish the competency to differentiate toward mesoderm. Our results suggest the ancient function of NANOG may be establishing the competence for lineage differentiation in early cells. These observations provide insights into embryonic development in the tetrapod ancestor from which terrestrial vertebrates evolved. The role of Nanog and Nodal in establishing pluripotency in an amphibian, the axolotl, indicates that the gene regulatory networks underlying pluripotency are conserved and provided the basis for the evolution of mesoderm.
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