BCAS2 is essential for hematopoietic stem and progenitor cell maintenance during zebrafish embryogenesis

Shanshan Yu, Tao Jiang, Danna Jia, Yunqiao Han, Fei Liu, Yuwen Huang, Zhen Qu, Yuntong Zhao, Jiayi Tu, Yuexia Lv, Jingzhen Li, Xuebin Hu, Zhaojing Lu, Shanshan Han, Yayun Qin, Xiliang Liu, Shanglun Xie, Qing K. Wang, Zhaohui Tang, Daji Luo and Mugen Liu

Key points

  • Bcas2 is a novel factor, required for HSPC maintenance in zebrafish embryos.

  • Bcas2 deletion triggers alternative splicing of Mdm4 and upregulation of p53 activation during HSPCs development.


Hematopoietic stem and progenitor cells (HSPCs) originate from the hemogenic endothelium via the endothelial-to-hematopoietic transition, are self-renewing, and replenish all lineages of blood cells throughout life. BCAS2 (breast carcinoma amplified sequence 2) is a component of the spliceosome and is involved in multiple biological processes. However, its role in hematopoiesis remains unknown. We established a bcas2 knockout zebrafish model by using transcription activator–like effector nucleases (TALENs). The bcas2-/- zebrafish showed severe impairment of HSPCs and their derivatives during definitive hematopoiesis. We also observed significant signs of HSPC apoptosis in the CHT of bcas2-/- zebrafish, which may be rescued by suppression of p53. Furthermore, we show that the bcas2 deletion induces an abnormal alternative splicing of Mdm4 that predisposes cells to undergo p53-mediated apoptosis, providing a mechanistic explanation of the deficiency observed in HSPC. Our findings revealed a novel and vital role for BCAS2 during HSPC maintenance in zebrafish.

  • Submitted September 26, 2018.
  • Accepted November 16, 2018.