生物
生殖系
DNA甲基化
重编程
体细胞
胚胎干细胞
表观遗传学
细胞分化
染色质
遗传学
细胞生物学
干细胞
DNA
细胞
基因
基因表达
作者
Mathieu Schulz,Aurélie Teissandier,Elena de la Mata,Mélanie Armand,Julian Iranzo,Fatima El Marjou,Pierre Gestraud,Marius Walter,Sarah Kinston,Berthold Göttgens,Max Greenberg,Déborah Bourc’his
标识
DOI:10.1101/2022.10.22.513040
摘要
ABSTRACT Somatic DNA methylation is established early during mammalian development, as embryonic cells transition from naive to primed pluripotency. This precedes the emergence of the three somatic germ layers, but also the segregation of the germline that undergoes genome-wide DNA demethylation after specification. While DNA methylation is essential for embryogenesis, the point at which it becomes critical during differentiation and whether all lineages equally depend on it is unclear. Using culture modeling of cellular transitions, we found that DNA methylation-free embryonic stem cells (ESCs) with a triple DNA methyltransferase knockout (TKO) normally progressed through the continuum of pluripotency states, but demonstrated skewed differentiation abilities towards neural versus other somatic lineages. More saliently, TKO ESCs were fully competent for establishing primordial germ cell-like cells (PGCLCs), even showing temporally extended and self-sustained capacity for the germline fate. By mapping chromatin states, we found that the neural and germline lineages are linked by a similar enhancer dynamics during priming, defined by common sets of methyl-sensitive transcription factors that fail to be decommissioned in absence of DNA methylation. We propose that DNA methylation controls the temporality of a coordinated neural-germline axis of preferred differentiation route during early development.
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