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

Kimberly Gwin, Joseph J. Dolence, Mariya B. Shapiro, Kay L Medina

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 hoxa9-/- mice. Interestingly, the reduction in Flt3+IL-7R+ CLPs in hoxa9-/- 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 hoxa9-/- 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.

Original languageEnglish (US)
Article number5
JournalBMC Immunology
Volume14
Issue number1
DOIs
StatePublished - Jan 30 2013

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Lymphoid Progenitor Cells
Bone Marrow
B-Lymphoid Precursor Cells
Natural Killer Cells
Bone Marrow Cells
Dendritic Cells
Homeostasis
B-Lymphocytes
Transcription Factors

Keywords

  • B-cell
  • DC
  • Development
  • Flt3
  • Hoxa9
  • IL-7R
  • NK-cell

ASJC Scopus subject areas

  • Immunology

Cite this

Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors. / Gwin, Kimberly; Dolence, Joseph J.; Shapiro, Mariya B.; Medina, Kay L.

In: BMC Immunology, Vol. 14, No. 1, 5, 30.01.2013.

Research output: Contribution to journalArticle

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