意大利帕多瓦大学Graziano Martello等研究人员合作发现，Esrrb引导原始多能细胞通过形成性转录程序。这一研究成果于2023年4月27日在线发表在国际学术期刊《自然—细胞生物学》上。

研究人员使用小鼠胚胎干细胞模型显示，ESRRB是激活形成性基因的必要条件和充分条件。Esrrb的遗传失活导致中胚层和胚胎外标志物的异常表达，形成性表达受损，以及不能在三维中自我组织。在功能上，这导致在没有Esrrb的情况下产生形成性干细胞和原始生殖细胞的能力受损。计算模型和基因组分析显示，ESRRB在原始细胞和整个形成态中占据了关键的形成性基因。这样一来，ESRRB启动了形成期的过渡，导致及时和无偏倚的多谱系分化能力。

据介绍，在胚胎发育过程中，原始多能上胚层细胞过渡到形成状态。形成期的外胚层细胞形成一个极化的上皮细胞，表现出不同的转录和表观遗传特征，并获得分化为所有体细胞和生殖系的能力。然而，人们对向形成态的过渡是如何被分子控制的了解有限。

附：英文原文

Title: Esrrb guides naive pluripotent cells through the formative transcriptional programme

Author: Carbognin, Elena, Carlini, Valentina, Panariello, Francesco, Chieregato, Martina, Guerzoni, Elena, Benvegn, Davide, Perrera, Valentina, Malucelli, Cristina, Cesana, Marcella, Grimaldi, Antonio, Mutarelli, Margherita, Carissimo, Annamaria, Tannenbaum, Eitan, Kugler, Hillel, Hackett, Jamie A., Cacchiarelli, Davide, Martello, Graziano

Issue&Volume: 2023-04-27

Abstract: During embryonic development, naive pluripotent epiblast cells transit to a formative state. The formative epiblast cells form a polarized epithelium, exhibit distinct transcriptional and epigenetic profiles and acquire competence to differentiate into all somatic and germline lineages. However, we have limited understanding of how the transition to a formative state is molecularly controlled. Here we used murine embryonic stem cell models to show that ESRRB is both required and sufficient to activate formative genes. Genetic inactivation of Esrrb leads to illegitimate expression of mesendoderm and extra-embryonic markers, impaired formative expression and failure to self-organize in 3D. Functionally, this results in impaired ability to generate formative stem cells and primordial germ cells in the absence of Esrrb. Computational modelling and genomic analyses revealed that ESRRB occupies key formative genes in naive cells and throughout the formative state. In so doing, ESRRB kickstarts the formative transition, leading to timely and unbiased capacity for multi-lineage differentiation.

DOI: 10.1038/s41556-023-01131-x

Source: https://www.nature.com/articles/s41556-023-01131-x