Loss of Resf1 reduces the efficiency of embryonic stem cell self-renewal and germline entry.
Loss of Resf1 reduces the efficiency of embryonic stem cell self-renewal and germline entry.
复制标题
RESF1的丢失降低了胚胎干细胞自我更新和种系的效率。
DOI：
10.26508/lsa.202101190
复制
发表时间：
2021-12
影响因子：
4.4
通讯作者：
Chambers I
中科院分区：
文献类型：
--
作者：
Vojtek M;Chambers I
RESF1通过增加跨膜LIF受体和关键的多潜能转录因子的表达来支持ESC的自我更新，并提高体外原始生殖细胞的分化效率。反转录元件沉默因子1(RESF1)与小鼠胚胎干细胞(ESCs)OCT4和NANOG的关键调控因子相互作用，其缺失导致小鼠不育。然而，RESF1在胚胎干细胞和生殖系规范中的功能还知之甚少。在这项研究中，我们使用Resf1基因敲除细胞系来确定RESF1对胚胎干细胞自我更新的需求，并在体外将胚胎干细胞定向为原始生殖细胞样细胞(PGCL)。我们发现，在血清和LIF培养的ESCs中，Resf1基因的缺失降低了ESC的自我更新能力，而RESF1的异体表达对ESC的自我更新有一定的积极作用。此外，在没有LIF的情况下，NANOG及其下游目标Esrrb推动自我更新的能力不需要RESF1。然而，Resf1的缺失降低了PGCLC的体外分化效率。这些结果证实了Resf1在多能干细胞和生殖细胞规范的调节中是一个新的参与者。
RESF1 supports ESC self-renewal by raising expression of transmembrane LIF receptor and key pluripotency transcription factors and increases in vitro primordial germ cell differentiation efficiency. Retroelement silencing factor 1 (RESF1) interacts with the key regulators of mouse embryonic stem cells (ESCs) OCT4 and NANOG, and its absence results in sterility of mice. However, the function of RESF1 in ESCs and germline specification is poorly understood. In this study, we used Resf1 knockout cell lines to determine the requirements of RESF1 for ESC self-renewal and for in vitro specification of ESCs into primordial germ cell-like cells (PGCLCs). We found that deletion of Resf1 in ESCs cultured in serum and LIF reduces self-renewal potential, whereas episomal expression of RESF1 has a modest positive effect on ESC self-renewal. In addition, RESF1 is not required for the capacity of NANOG and its downstream target ESRRB to drive self-renewal in the absence of LIF. However, Resf1 deletion reduces the efficiency of PGCLC differentiation in vitro. These results identify Resf1 as a novel player in the regulation of pluripotent stem cells and germ cell specification.