title: Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo.
abstract: Bcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested this hypothesis by analyzing the development of DC and other lineages in Bcl11a (-/-) mice. We found that Bcl11a was required for expression of IL-7 receptor (IL-7R) and Flt3 in early hematopoietic progenitor cells. In addition, we found severely decreased numbers of plasmacytoid dendritic cells (pDCs) in Bcl11a (-/-) fetal livers and in the bone marrow of Bcl11a (-/-) fetal liver chimeras. Moreover, Bcl11a (-/-) cells showed severely impaired in vitro development of Flt3L-derived pDCs and classical DCs (cDCs). In contrast, we found normal in vitro development of DCs from Bcl11a (-/-) fetal liver cells treated with GM-CSF. These results suggest that the persistent cDC development observed in Bcl11a (-/-) fetal liver chimeras reflects derivation from a Bcl11a- and Flt3-independent pathway in vivo.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.forename: Wumesh
authors.initials: W
authors.lastname: Kc
authors.forename: Pentao
authors.initials: P
authors.lastname: Liu
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016130:Immunophenotyping; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: C407733:Bcl11a protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051941:fms-Like Tyrosine Kinase 3