title: The BAF45a/PHF10 subunit of SWI/SNF-like chromatin remodeling complexes is essential for hematopoietic stem cell maintenance.
abstract: The ability of hemopoietic stem cells to self-renew and differentiate into downstream lineages is dependent on specialized chromatin environments that establish and maintain stage-specific patterns of gene expression. However, the epigenetic factors responsible for mediating these regulatory events remain poorly defined. Here we provide evidence that BAF45a/PHF10, a subunit of SWI/SNF-like chromatin remodeling complexes, is essential for adult hemopoietic stem cell maintenance and myeloid lineage development. Deletion of BAF45a in the mouse is embryonic lethal. Acute deletion of BAF45a in the adult hemopoietic system causes a dose-dependent decrease in the frequency of long-term repopulating hemopoietic stem cells and committed myeloid progenitors without affecting their rate of proliferation. BAF45a-deficient hemopoietic stem cells and myeloid progenitors are selectively lost from mixed bone marrow chimeras, indicating their impaired function even in an intact microenvironment. Together, these studies suggest that the BAF45a subunit of SWI/SNF-like chromatin remodeling complexes plays nonredundant and specialized roles within the developing hemopoietic tissue.
authors.affiliation: IRIC, Institute for Research in Immunology and Cancer, Montreal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Veneta
authors.initials: V
authors.lastname: Krasteva
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA; Developmental Biology, Stanford University School of Medicine, Stanford, CA.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
authors.affiliation: IRIC, Institute for Research in Immunology and Cancer, Montreal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada. Electronic address: j.lessard.1@umontreal.ca.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lessard
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D023061:Gene Order; D005804:Genes, Lethal; D056426:Genetic Loci; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D015533:Transcriptional Activation; D016335:Zinc Fingers
chemical_list: D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits