Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation

Yang Chen; Yukang Wu; Jianguo Li; Kai Chen; Wuchan Wang; Zihui Ye; Ke Feng; Yiwei Yang; Yanxin Xu; Jiuhong Kang; Xudong Guo

doi:10.1038/s41420-023-01548-1

Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation

Cell Death Discov. 2023 Jul 14;9(1):244. doi: 10.1038/s41420-023-01548-1.

Authors

Yang Chen^#¹, Yukang Wu^#¹, Jianguo Li¹, Kai Chen¹, Wuchan Wang¹, Zihui Ye¹, Ke Feng¹, Yiwei Yang¹, Yanxin Xu¹, Jiuhong Kang², Xudong Guo^{3

4}

Affiliations

¹ 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.
² 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. jhkang@tongji.edu.cn.
³ 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. 19504@tongji.edu.cn.
⁴ Institute for Advanced Study, Tongji University, Shanghai, 200092, China. 19504@tongji.edu.cn.

^# Contributed equally.

Abstract

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.

Abstract

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