TY - JOUR
T1 - Mitochondrial Protein Synthesis Is Essential for Terminal Differentiation of CD45– TER119–Erythroid and Lymphoid Progenitors
AU - Gotoh, Kazuhito
AU - Kunisaki, Yuya
AU - Mizuguchi, Soichi
AU - Setoyama, Daiki
AU - Hosokawa, Kentaro
AU - Yao, Hisayuki
AU - Nakashima, Yuya
AU - Yagi, Mikako
AU - Uchiumi, Takeshi
AU - Semba, Yuichiro
AU - Nogami, Jumpei
AU - Akashi, Koichi
AU - Arai, Fumio
AU - Kang, Dongchon
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Numbers JP18K11077 and JP16K19196 to K.G., JP18H02841 to Y.K., JP17H04208 and JP19K22638 to F.A., JP15H04764 and JP24590387 to T.U., JP20H00530 and JP17H01550 to D.K.. This work was supported by a grant from the Takeda Science Foundation (to K.G. and Y. K.). We would like to acknowledge all of our colleagues in Dr. Kang's and Dr. Arai's laboratory for their support throughout this project. We appreciate the technical support from the Research Support Center, Graduate School of Medical Sciences, Kyushu University, and the Medical Institute of Bioregulation, Kyushu University. We thank R. Ugawa for performing the transmission electron microscopic observations. We also thank M. Arico from Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 Kyushu University
PY - 2020/11/20
Y1 - 2020/11/20
N2 - p32/C1qbp regulates mitochondrial protein synthesis and is essential for oxidative phosphorylation in mitochondria. Although dysfunction of p32/C1qbp impairs fetal development and immune responses, its role in hematopoietic differentiation remains unclear. Here, we found that mitochondrial dysfunction affected terminal differentiation of newly identified erythroid/B-lymphoid progenitors among CD45– Ter119– CD31– triple-negative cells (TNCs) in bone marrow. Hematopoietic cell-specific genetic deletion of p32/C1qbp (p32cKO) in mice caused anemia and B-lymphopenia without reduction of hematopoietic stem/progenitor cells. In addition, p32cKO mice were susceptible to hematopoietic stress with delayed recovery from anemia. p32/C1qbp-deficient CD51– TNCs exhibited impaired mitochondrial oxidation that consequently led to inactivation of mTORC1 signaling, which is essential for erythropoiesis. These findings uncover the importance of mitochondria, especially at the stage of TNCs during erythropoiesis, suggesting that dysregulation of mitochondrial protein synthesis is a cause of anemia and B-lymphopenia with an unknown pathology.
AB - p32/C1qbp regulates mitochondrial protein synthesis and is essential for oxidative phosphorylation in mitochondria. Although dysfunction of p32/C1qbp impairs fetal development and immune responses, its role in hematopoietic differentiation remains unclear. Here, we found that mitochondrial dysfunction affected terminal differentiation of newly identified erythroid/B-lymphoid progenitors among CD45– Ter119– CD31– triple-negative cells (TNCs) in bone marrow. Hematopoietic cell-specific genetic deletion of p32/C1qbp (p32cKO) in mice caused anemia and B-lymphopenia without reduction of hematopoietic stem/progenitor cells. In addition, p32cKO mice were susceptible to hematopoietic stress with delayed recovery from anemia. p32/C1qbp-deficient CD51– TNCs exhibited impaired mitochondrial oxidation that consequently led to inactivation of mTORC1 signaling, which is essential for erythropoiesis. These findings uncover the importance of mitochondria, especially at the stage of TNCs during erythropoiesis, suggesting that dysregulation of mitochondrial protein synthesis is a cause of anemia and B-lymphopenia with an unknown pathology.
UR - http://www.scopus.com/inward/record.url?scp=85092923591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092923591&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101654
DO - 10.1016/j.isci.2020.101654
M3 - Article
AN - SCOPUS:85092923591
VL - 23
JO - iScience
JF - iScience
SN - 2589-0042
IS - 11
M1 - 101654
ER -