title: Loss of autophagy leads to failure in megakaryopoiesis, megakaryocyte differentiation, and thrombopoiesis in mice.
abstract: During hematopoiesis, megakaryopoiesis, megakaryocyte differentiation, and thrombopoiesis are regulated at multiple stages, which involve successive lineage commitment steps and proceed with polyploidization, maturation, and organized fragmentation of the cytoplasm, leading to the release of platelets in circulation. However, the cellular mechanisms by which megakaryocytes derive from their progenitors and differentiate into platelets have not fully been understood. Using an Atg7 hematopoietic conditional knockout mouse model, we found that loss of autophagy, a metabolic process essential in homeostasis and cellular remodeling, caused mitochondrial and cell cycle dysfunction, impeding megakaryopoiesis and megakaryocyte differentiation, as well as thrombopoiesis and subsequently produced abnormal platelets, larger in size and fewer in number, ultimately leading to severely impaired platelet production and failed hemostasis.
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Cai
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yuan
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Menglin
authors.initials: M
authors.lastname: Shang
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Affiliated Children's Hospital, Soochow University School of Medicine, Suzhou, China. Electronic address: jrwang@suda.edu.cn.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D005260:Female; D008297:Male; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D016133:Polymerase Chain Reaction; D034061:Thrombopoiesis
chemical_list: D017931:DNA Primers