title: Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis.
abstract: Epigenetic regulators play critical roles in normal hematopoiesis, and the activity of these enzymes is frequently altered in hematopoietic cancers. The major type II protein arginine methyltransferase PRMT5 catalyzes the formation of symmetric dimethyl arginine and has been implicated in various cellular processes, including pluripotency and tumorigenesis. Here, we generated Prmt5 conditional KO mice to evaluate the contribution of PRMT5 to adult hematopoiesis. Loss of PRMT5 triggered an initial but transient expansion of hematopoietic stem cells (HSCs); however, Prmt5 deletion resulted in a concurrent loss of hematopoietic progenitor cells (HPCs), leading to fatal BM aplasia. PRMT5-specific effects on hematopoiesis were cell intrinsic and depended on PRMT5 methyltransferase activity. We found that PRMT5-deficient hematopoietic stem and progenitor cells exhibited severely impaired cytokine signaling as well as upregulation of p53 and expression of its downstream targets. Together, our results demonstrate that PRMT5 plays distinct roles in the behavior of HSCs compared with HPCs and is essential for the maintenance of adult hematopoietic cells.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Guoyan
authors.initials: G
authors.lastname: Cheng
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Hamard
authors.forename: Sarah
authors.initials: S
authors.lastname: Greenblatt
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Man
authors.forename: Fabiana
authors.initials: F
authors.lastname: Perna
authors.forename: Haiming
authors.initials: H
authors.lastname: Xu
authors.forename: Madhavi
authors.initials: M
authors.lastname: Tadi
authors.forename: Luisa
authors.initials: L
authors.lastname: Luciani
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000818:Animals; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016159:Tumor Suppressor Protein p53; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases