Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors

<p>Abstract</p> <p>Hoxa9 is a homeodomain transcription factor important for the generation of Flt3+hiIL-7R- lymphoid biased-multipotential progenitors, Flt3+IL-7R+ common lymphoid progenitors (CLPs), and B cell precursors (BCP) in bone marrow (BM). In addition to B-cell, Flt3+IL-7...

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Main Authors: Gwin Kimberly, Dolence Joseph J, Shapiro Mariya B, Medina Kay L
Format: Article
Language:English
Published: BMC 2013-01-01
Series:BMC Immunology
Subjects:
Online Access:http://www.biomedcentral.com/1471-2172/14/5
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author Gwin Kimberly
Dolence Joseph J
Shapiro Mariya B
Medina Kay L
author_facet Gwin Kimberly
Dolence Joseph J
Shapiro Mariya B
Medina Kay L
author_sort Gwin Kimberly
collection DOAJ
description <p>Abstract</p> <p>Hoxa9 is a homeodomain transcription factor important for the generation of Flt3+hiIL-7R- lymphoid biased-multipotential progenitors, Flt3+IL-7R+ common lymphoid progenitors (CLPs), and B cell precursors (BCP) in bone marrow (BM). In addition to B-cell, Flt3+IL-7R+ CLPs possess NK and DC developmental potentials, although DCs arise from Flt3+IL-7R- myeloid progenitors as well. In this study, we investigated the requirement for Hoxa9, from Flt3+ or Flt3- progenitor subsets, in the development of NK and DC lineage cells in BM. Flt3+IL-7R+Ly6D- CLPs and their Flt3+IL-7R+Ly6D+ B lineage-restricted progeny (BLP) were significantly reduced in <it>hoxa9−/−</it> mice. Interestingly, the reduction in Flt3+IL-7R+ CLPs in <it>hoxa9−/−</it> mice had no impact on the generation of NK precursor (NKP) subsets, the differentiation of NKP into mature NK cells, or NK homeostasis. Similarly, percentages and numbers of common dendritic progenitors (CDP), as well as their plasmacytoid or conventional dendritic cell progeny in <it>hoxa9−/−</it> mice were comparable to wildtype. These findings reveal distinct requirements for Hoxa9 or Hoxa9/Flt3 molecular circuits in regulation of B versus NK and DC development in BM.</p>
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spelling doaj.art-1dd8b66020514436b53b8657e1fc2d1a2022-12-21T22:39:51ZengBMCBMC Immunology1471-21722013-01-01141510.1186/1471-2172-14-5Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitorsGwin KimberlyDolence Joseph JShapiro Mariya BMedina Kay L<p>Abstract</p> <p>Hoxa9 is a homeodomain transcription factor important for the generation of Flt3+hiIL-7R- lymphoid biased-multipotential progenitors, Flt3+IL-7R+ common lymphoid progenitors (CLPs), and B cell precursors (BCP) in bone marrow (BM). In addition to B-cell, Flt3+IL-7R+ CLPs possess NK and DC developmental potentials, although DCs arise from Flt3+IL-7R- myeloid progenitors as well. In this study, we investigated the requirement for Hoxa9, from Flt3+ or Flt3- progenitor subsets, in the development of NK and DC lineage cells in BM. Flt3+IL-7R+Ly6D- CLPs and their Flt3+IL-7R+Ly6D+ B lineage-restricted progeny (BLP) were significantly reduced in <it>hoxa9−/−</it> mice. Interestingly, the reduction in Flt3+IL-7R+ CLPs in <it>hoxa9−/−</it> mice had no impact on the generation of NK precursor (NKP) subsets, the differentiation of NKP into mature NK cells, or NK homeostasis. Similarly, percentages and numbers of common dendritic progenitors (CDP), as well as their plasmacytoid or conventional dendritic cell progeny in <it>hoxa9−/−</it> mice were comparable to wildtype. These findings reveal distinct requirements for Hoxa9 or Hoxa9/Flt3 molecular circuits in regulation of B versus NK and DC development in BM.</p>http://www.biomedcentral.com/1471-2172/14/5Hoxa9Flt3IL-7RB-cellNK-cellDCDevelopment
spellingShingle Gwin Kimberly
Dolence Joseph J
Shapiro Mariya B
Medina Kay L
Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
BMC Immunology
Hoxa9
Flt3
IL-7R
B-cell
NK-cell
DC
Development
title Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
title_full Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
title_fullStr Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
title_full_unstemmed Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
title_short Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors
title_sort differential requirement for hoxa9 in the development and differentiation of b nk and dc lineage cells from flt3 multipotential progenitors
topic Hoxa9
Flt3
IL-7R
B-cell
NK-cell
DC
Development
url http://www.biomedcentral.com/1471-2172/14/5
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