FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells.
Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs.
Liu
Fei
F
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Lee
Jae Y
JY
Wei
Huijun
H
Tanabe
Osamu
O
Engel
James D
JD
Morrison
Sean J
SJ
Guan
Jun-Lin
JL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism; D005333:Fetus; D005434:Flow Cytometry; D005838:Genotype; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; C428743:Rb1cc1 protein, mouse