title: The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function.
abstract: ATP-dependent SWI/SNF-like BAF chromatin remodeling complexes are emerging as key regulators of embryonic and adult stem cell function. Particularly intriguing are the findings that specialized assemblies of BAF complexes are required for establishing and maintaining pluripotent and multipotent states in cells. However, little is known on the importance of these complexes in normal and leukemic hemopoiesis. Here we provide the first evidence that the actin-related protein BAF53a, a subunit of BAF complexes preferentially expressed in long-term repopulating stem cells, is essential for adult hemopoiesis. Conditional deletion of BAF53a resulted in multilineage BM failure, aplastic anemia, and rapid lethality. These severe hemopoietic defects originate from a proliferative impairment of BM HSCs and progenitors and decreased progenitor survival. Using hemopoietic chimeras, we show that the impaired function of BAF53a-deficient HSCs is cell-autonomous and independent of the BM microenvironment. Altogether, our studies highlight an unsuspected role for BAF chromatin remodeling complexes in the maintenance of HSC and progenitor cell properties.
authors.affiliation: Institute for Research in Immunology and Cancer (IRIC), Montreal, QC.
authors.forename: Veneta
authors.initials: V
authors.lastname: Krasteva
authors.forename: Manuel
authors.initials: M
authors.lastname: Buscarlet
authors.forename: Abigail
authors.initials: A
authors.lastname: Diaz-Tellez
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Bernard
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lessard
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000741:Anemia, Aplastic / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D006413:Hematopoietic System / Q000254:growth & development / Q000378:metabolism*; D008099:Liver; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D000199:Actins; C485486:Actl6a protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins