Chen Yang, Wu Yukang, Li Jianguo, Chen Kai, Wang Wuchan, Ye Zihui, Feng Ke, Yang Yiwei, Xu Yanxin, Kang Jiuhong, Guo Xudong
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Institute for Advanced Study, Tongji University, Shanghai, 200092, China.
Cell Death Discov. 2023 Jul 14;9(1):244. doi: 10.1038/s41420-023-01548-1.
The zinc finger proteins (ZNFs) mediated transcriptional regulation is critical for cell fate transition. However, it is still unclear how the ZNFs realize their specific regulatory roles in the stage-specific determination of cardiomyocyte differentiation. Here, we reported that the zinc fingers and homeoboxes 1 (Zhx1) protein, transiently expressed during the cell fate transition from mesoderm to cardiac progenitors, was indispensable for the proper cardiomyocyte differentiation of mouse and human embryonic stem cells. Moreover, Zhx1 majorly promoted the specification of cardiac progenitors via interacting with hnRNPA1 and co-activated the transcription of a wide range of genes. In-depth mechanistic studies showed that Zhx1 was bound with hnRNPA1 by the amino acid residues (Thr111-His120) of the second Znf domain, thus participating in the formation of cardiac progenitors. Together, our study highlights the unrevealed interaction of Zhx1/hnRNPA1 for activating gene transcription during cardiac progenitor specification and also provides new evidence for the specificity of cell fate determination in cardiomyocyte differentiation.
锌指蛋白（ZNFs）介导的转录调控对于细胞命运转变至关重要。然而，ZNFs如何在心肌细胞分化的阶段特异性决定中发挥其特定的调控作用仍不清楚。在此，我们报道了锌指和同源框1（Zhx1）蛋白，在从中胚层到心脏祖细胞的细胞命运转变过程中短暂表达，对于小鼠和人类胚胎干细胞的正常心肌细胞分化是不可或缺的。此外，Zhx1主要通过与hnRNPA1相互作用促进心脏祖细胞的特化，并共同激活多种基因的转录。深入的机制研究表明，Zhx1通过第二个Znf结构域的氨基酸残基（Thr111-His120）与hnRNPA1结合，从而参与心脏祖细胞的形成。总之，我们的研究突出了Zhx1/hnRNPA1在心脏祖细胞特化过程中激活基因转录的未被揭示的相互作用，也为心肌细胞分化中细胞命运决定的特异性提供了新证据。
