南方科技大学Andrew P. Hutchins等研究人员合作发现，核基质在人体多能干细胞中稳定特定启动基因。这一研究成果于2025年1月9日在线发表在国际学术期刊《自然—细胞生物学》上。

研究人员发现，通过破坏异质核核糖核蛋白U（HNRNPU）或核基质蛋白Matrin-3，初始状态的人体多能干细胞（hPSC）表现出与naïve多能状态相似的特征，包括形态学变化和naïve特异性标记基因的上调。研究人员证明，HNRNPU的耗竭导致染色质可接近性增加，DNA接触减少和细胞核大小增加。

在机制上，HNRNPU作为转录辅因子，协同POLII将初始特异性基因的启动子锚定到核基质上，促进其表达及RNA稳定性。总体而言，HNRNPU促进细胞类型的稳定性，当其减少时，会促进向更早期胚胎状态的转化。

据介绍，核基质是一种由蛋白质和RNA组成的蛋白质凝胶，是支持染色质结构的重要核结构，但其在hPSC中的作用尚未被描述。

附：英文原文

Title: The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells

Author: Ma, Gang, Fu, Xiuling, Zhou, Lulu, Babarinde, Isaac A., Shi, Liyang, Yang, Wenting, Chen, Jiao, Xiao, Zhen, Qiao, Yu, Ma, Lisha, Ou, Yuhao, Li, Yuhao, Chang, Chen, Deng, Boping, Zhang, Ran, Sun, Li, Tong, Guoqing, Li, Dongwei, Li, Yiming, Hutchins, Andrew P.

Issue&Volume: 2025-01-09

Abstract: The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that HNRNPU depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size. Mechanistically, HNRNPU acts as a transcriptional co-factor that anchors promoters of primed-specific genes to the nuclear matrix with POLII to promote their expression and their RNA stability. Overall, HNRNPU promotes cell-type stability and when reduced promotes conversion to earlier embryonic states.

DOI: 10.1038/s41556-024-01595-5

Source: https://www.nature.com/articles/s41556-024-01595-5