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体内可视化小鼠原始生殖细胞中的 X 染色体重新激活。

Visualization of X chromosome reactivation in mouse primordial germ cells in vivo.

机构信息

Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.

Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koutou-ku, Tokyo 135-0064, Japan.

出版信息

Biol Open. 2021 Apr 15;10(4). doi: 10.1242/bio.058602. Epub 2021 Apr 29.

Abstract

X chromosome inactivation (XCI), determined during development, remains stable after embryonic cell divisions. However, primordial germ cells (PGCs) are exceptions in that XCI is reprogrammed and inactivated X chromosomes are reactivated. Although interactions between PGCs and somatic cells are thought to be important for PGC development, little is known about them. Here, we performed imaging of X chromosome reactivation (XCR) using the 'Momiji' mouse system, which can monitor the X chromosome's inactive and active states using two color fluorescence reporter genes, and investigated whether interactions would affect XCR in PGCs. Based on their expression levels, we found that XCR of the Pgk1 locus began at embryonic day (E)10.5 and was almost complete by E13.5. During this period, PGCs became distributed uniformly in the genital ridge, proliferated, and formed clusters; XCR progressed accordingly. In addition, XCR of the Pgk1 locus preceded that of the Hprt locus, indicating that the timing of epigenetic memory erasure varied according to the locus of each of these X-linked genes. Our results indicate that XCR proceeds along with the proliferation of PGCs clustered within the genital ridge. This article has an associated First Person interview with the first author of the paper.

摘要

X 染色体失活(XCI)在发育过程中确定,在胚胎细胞分裂后仍然稳定。然而,原始生殖细胞(PGC)是例外,因为 XCI 会被重新编程,失活的 X 染色体被重新激活。尽管 PGC 与体细胞之间的相互作用被认为对 PGC 的发育很重要,但人们对此知之甚少。在这里,我们使用“Momiji”小鼠系统进行了 X 染色体重新激活(XCR)的成像研究,该系统可以使用两种颜色荧光报告基因监测 X 染色体的失活和激活状态,并研究相互作用是否会影响 PGC 中的 XCR。根据它们的表达水平,我们发现 Pgk1 基因座的 XCR 始于胚胎期(E)10.5 天,到 E13.5 天时几乎完全完成。在此期间,PGC 均匀分布在生殖嵴中,增殖并形成簇;XCR 相应地进展。此外,Pgk1 基因座的 XCR 先于 Hprt 基因座,表明表观遗传记忆擦除的时间根据这些 X 连锁基因的每个基因座的位置而有所不同。我们的结果表明,XCR 伴随着生殖嵴内聚集的 PGC 的增殖进行。本文有该论文第一作者的相关第一人称采访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aad3/8096617/6ec0c452089d/biolopen-10-058602-g1.jpg

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