title: FIP200, an essential component of mammalian autophagy is indispensible for fetal hematopoiesis.
abstract: Autophagy, an evolutionarily conserved cellular process for bulk protein degradation through lysosomes, plays important roles in various physiological and pathological processes. Recent studies suggest that autophagy also participates in erythroid development. However, to what extent autophagy is involved in hematopoiesis is largely unknown. FIP200 (focal adhesion kinase family interacting protein of 200 kD) is a newly identified essential autophagy gene and a component of the ULK-Atg13-FIP200 complex. We show that mice lacking FIP200 in hematopoietic cells (CKO mice) experience perinatal lethality associated with severe erythroblastic anemia. FIP200 is cell-autonomously required for the maintenance and function of fetal hematopoietic stem cells (HSCs). FIP200 deletion in HSCs does not result in increased apoptosis. However, aberrantly increased HSC proliferation and myeloid expansion are found in CKO embryos, which may be responsible for the depletion of fetal HSCs. Consistent with an essential role of FIP200 in autophagy, FIP200-null fetal HSCs as well as other hematopoietic cells exhibit increased mitochondria mass and reactive oxygen species (ROS). Together, our data identify FIP200 as a key intrinsic regulator of fetal HSCs and suggest a role of autophagy in fetal hematopoiesis and the maintenance of fetal HSCs.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D005333:Fetus / Q000166:cytology* / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008322:Mammals / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; C428743:Rb1cc1 protein, mouse