Rif1 和 Hmgn3 调节小鼠滋养层干细胞的转化。

Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells.

机构信息

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China; Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Health Center for Women and Children, Chongqing 400013, China.

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China.

出版信息

Cell Rep. 2022 Mar 29;38(13):110570. doi: 10.1016/j.celrep.2022.110570.

DOI:10.1016/j.celrep.2022.110570

PMID:35354046

Abstract

The appearance of trophectoderm (TE) is a hallmark event in preimplantation development during murine embryogenesis. However, little is known about the mechanisms underlying TE specification. We find that the depletion of Rif1 breaks down the barrier to the transition from embryonic stem cells (ESCs) to trophoblast stem cells (TSCs). Rif1-null-induced TSCs show typical TE properties and the potential to differentiate into terminal trophoblast lineages. Global transcriptome analysis reveal that Rif1 deletion activates 2-cell embryo (2C)-related genes and induces a totipotent-like state. Chimeric assays further confirm that Rif1-null ESCs contribute to the functional placenta in addition to the fetus on embryonic day 12.5. Furthermore, we show overexpression of Hmgn3, one of the key upregulated gene in Rif1-null ESCs, facilitates the induction of TSCs. Therefore, we report two key genes regulating the conversion of TSCs and provide insights for investigating TE specification.

摘要

滋养外胚层（TE）的出现是小鼠胚胎发生中胚胎植入前发育的一个标志性事件。然而，对于 TE 特化的机制知之甚少。我们发现 Rif1 的耗竭打破了从胚胎干细胞（ESCs）向滋养层干细胞（TSCs）过渡的障碍。 Rif1 缺失诱导的 TSCs 表现出典型的 TE 特性，并具有分化为终末滋养细胞谱系的潜力。全转录组分析显示 Rif1 缺失激活了 2 细胞胚胎（2C）相关基因，并诱导出全能性样状态。嵌合实验进一步证实，Rif1 缺失的 ESCs 除了在胚胎第 12.5 天形成功能性胎盘外，还能形成胎儿。此外，我们还发现 Rif1 缺失的 ESCs 中关键上调基因之一的 Hmgn3 的过表达有助于 TSCs 的诱导。因此，我们报告了两个关键基因，它们调节 TSCs 的转化，并为研究 TE 特化提供了思路。