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Activin A and BMP4 Signaling Expands Potency of Mouse Embryonic Stem Cells in Serum-Free Media.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-02-06 , DOI: 10.1016/j.stemcr.2020.01.004
Baojiang Wu 1 , Lin Li 2 , Bojiang Li 3 , Junpeng Gao 4 , Yanglin Chen 5 , Mengyi Wei 5 , Zhiqing Yang 5 , Baojing Zhang 5 , Shudong Li 6 , Kexin Li 7 , Changshan Wang 7 , M Azim Surani 8 , Xihe Li 1 , Fuchou Tang 9 , Siqin Bao 5
Affiliation  

Inhibitors of Mek1/2 and Gsk3β, known as 2i, and, together with leukemia inhibitory factor, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency (2i/L-ESCs). However, recent reports show that prolonged Mek1/2 suppression impairs developmental potential of ESCs, and is rescued by serum (S/L-ESCs). Here, we show that culturing ESCs in Activin A and BMP4, and in the absence of MEK1/2 inhibitor (ABC/L medium), establishes advanced stem cells derived from ESCs (esASCs). We demonstrate that esASCs contributed to germline lineages, full-term chimeras and generated esASC-derived mice by tetraploid complementation. We show that, in contrast to 2i/L-ESCs, esASCs display distinct molecular signatures and a stable hypermethylated epigenome, which is reversible and similar to serum-cultured ESCs. Importantly, we also derived novel ASCs (blASCs) from blastocysts in ABC/L medium. Our results provide insights into the derivation of novel ESCs with DNA hypermethylation from blastocysts in chemically defined medium.



中文翻译:

激活素A和BMP4信号传导可在无血清培养基中扩大小鼠胚胎干细胞的效力。

Mek1 / 2和Gsk3β的抑制剂(称为2i)与白血病抑制因子一起,可增强胚胎干细胞(ESC)的衍生并促进基态多能性(2i / L-ESC)。但是,最近的报道表明,长时间的Mek1 / 2抑制会损害ESC的发育潜能,并且可以通过血清(S / L-ESC)进行挽救。在这里,我们显示了在激活素A和BMP4中培养ESC,并且在没有MEK1 / 2抑制剂(ABC / L培养基)的情况下,可以建立源自ESC(esASC)的干细胞。我们证明esASCs有助于种系谱系,足月嵌合体和通过四倍体互补产生esASC衍生的小鼠。我们显示,与2i / L-ESCs相比,esASCs显示出独特的分子特征和稳定的高甲基化表观基因组,该基因组是可逆的并且类似于血清培养的ESCs。重要的,我们还从ABC / L培养基中的囊胚中获得了新型ASC(blASCs)。我们的结果提供了洞见,从化学定义的培养基中囊胚的DNA超甲基化的新型ESCs的派生。

更新日期:2020-02-06
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