title: ROS functions as an upstream trigger for autophagy to drive hematopoietic stem cell differentiation.
abstract: OBJECTIVE
  We have recently described a mechanistic action of autophagy on hematopoiesis in which autophagy sustains hematopoietic stem cell multilineage differentiation by direct targeting of intracellular Notch. However, the upstream signal that triggers autophagy to degrade Notch during hematopoiesis remains elusive.
  
  
  METHODS
  Conditional autophagy-essential gene Atg7 knockout mouse model is used for identifying signals regulating autophagy in the promotion of hematopoiesis.
  
  
  RESULTS
  We find here that generation of reactive oxygen species (ROS) is progressively increased during hematopoietic stem cell differentiation, and inhibition of ROS production was found to attenuate the differentiation of hematopoietic stem cells. In hematopoietic stem and progenitor cells (HSPCs) of wild-type mice, inhibition of ROS production downregulated autophagy activity but upregulated intracellular Notch and its downstream effectors. In contrast, in the HSPCs of autophagy fully defective mice, ROS inhibition did not alter myeloid differentiation, and hematopoietic stem cell differentiation to multi-lineages no longer responded to ROS inhibition.
  
  
  CONCLUSIONS
  The ROS-regulating hematopoiesis is mitochondrial origin, and this action depends on intact autophagy machinery capable of degrading intracellular Notch.
  
  
  CONCLUSIONS
  ROS functions as an upstream signal in the autophagic promotion of hematopoietic stem cell differentiation.
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Cai
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Na
authors.initials: N
authors.lastname: Yuan
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Suping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Jiangsu Key Laboratory for Stem Cell Research, Collaborative Innovation Center of Hematology , Soochow University School of Medicine , Suzhou , China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species
keywords: Autophagy; Hematopoietic stem cells; Notch; Reactive oxygen species