title: RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish.
abstract: Hematopoietic stem and progenitor cells (HSPCs) are capable of self-renewal and replenishing all lineages of blood cells throughout life and are thus crucial for tissue homeostasis. However, the mechanism regulating HSPC development is still incompletely understood. Here, we isolate a zebrafish mutant with defective T lymphopoiesis and positional cloning identifies that Rpc9, a component of DNA-directed RNA polymerase III (Pol III) complex, is responsible for the mutant phenotype. Further analysis shows that rpc9 deficiency leads to the impairment of HSPCs and their derivatives in zebrafish embryos. Excessive apoptosis is observed in the caudal hematopoietic tissue (CHT; the equivalent of fetal liver in mammals) of rpc9(-/-) embryos and the hematopoietic defects in these embryos can be fully rescued by suppression of p53 Thus, our work illustrates that Rpc9, a component of Pol III, plays an important tissue-specific role in HSPC maintenance during zebrafish embryogenesis and might be conserved across vertebrates, including mammals.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yonglong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Cell Biology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China liuf@ioz.ac.cn.
authors.forename: Feng
authors.identifier: 0000-0003-3228-0943
authors.initials: F
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival; D004625:Embryo, Nonmammalian / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012320:RNA Polymerase III / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D012320:RNA Polymerase III; C000622222:crcp protein, zebrafish
keywords: Hematopoietic stem and progenitor cells; P53; RNA polymerase III; Rpc9; Zebrafish