PUBLICATION
BCAS2 is essential for hematopoietic stem and progenitor cell maintenance during zebrafish embryogenesis
- Authors
- Yu, S., Jiang, T., Jia, D., Han, Y., Liu, F., Huang, Y., Qu, Z., Zhao, Y., Tu, J., Lv, Y., Li, J., Hu, X., Lu, Z., Han, S., Qin, Y., Liu, X., Xie, S., Wang, Q.K., Tang, Z., Luo, D., Liu, M.
- ID
- ZDB-PUB-181130-2
- Date
- 2018
- Source
- Blood 133(8): 805-815 (Journal)
- Registered Authors
- Han, Shanshan, Huang, Yuwen, Hu, Xuebin, Li, Jingzhen, Liu, Fei, Liu, Mugen, Liu, Xiliang, Lu, Zhaojing, Qin, Yayun, Qu, Zhen, Yu, Shanshan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/embryology
- Animals, Genetically Modified/genetics
- Embryo, Nonmammalian/embryology*
- Embryonic Development*
- Gene Knockdown Techniques
- Hematopoietic Stem Cells/metabolism*
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30482793 Full text @ Blood
Citation
Yu, S., Jiang, T., Jia, D., Han, Y., Liu, F., Huang, Y., Qu, Z., Zhao, Y., Tu, J., Lv, Y., Li, J., Hu, X., Lu, Z., Han, S., Qin, Y., Liu, X., Xie, S., Wang, Q.K., Tang, Z., Luo, D., Liu, M. (2018) BCAS2 is essential for hematopoietic stem and progenitor cell maintenance during zebrafish embryogenesis. Blood. 133(8):805-815.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping