ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Hoxa9 and Flt3 signaling synergistically regulate an early checkpoint in lymphopoiesis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Activating an interleukin 4-FLT3-STAT6 axis in multipotent progenitors restores lymphopoiesis in inflammation and aging.Immunity · 2026Article
- Unlocking the HOX: Homeobox Genes as Regulators of Hematopoietic Development.International journal of molecular sciences · 2026Review
- T cell development from expanded hematopoietic progenitors reveals initiation control byScience immunology · 2026Article
- Tubular epithelial cell-derived Flt3L is required for type 1 conventional dendritic cell (cDC1) activation and expansion in promoting the recovery in acute kidney injury.Journal of advanced research · 2025Article
- Single-cell profiling unveils a geroprotective role of Procyanidin C1 in hematopoietic immune system via senolytic and senomorphic effects.npj aging · 2025Article
- HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.Journal of applied genetics · 2024Review
- FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.Cell · 2024Article
- Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.Frontiers in immunology · 2023Review
- CDX-301 prevents radiation-induced dysregulation of miRNA expression and biogenesis.Molecular therapy. Nucleic acids · 2022Article
- Flt3 Signaling in B Lymphocyte Development and Humoral Immunity.International journal of molecular sciences · 2022Review
- Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma.Scientific reports · 2020Article
- CDX-301: a novel medical countermeasure for hematopoietic acute radiation syndrome in mice.Scientific reports · 2020Article
- Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors.Cell research · 2020Article
- Single-Cell Analysis Reveals Regulatory Gene Expression Dynamics Leading to Lineage Commitment in Early T Cell Development.Cell systems · 2019Article
- Developmental and Functional Control of Natural Killer Cells by Cytokines.Frontiers in immunology · 2017Review
- Developmental stage-specific effects of Pim-1 dysregulation on murine bone marrow B cell development.BMC immunology · 2016Article
- Cell extrinsic alterations in splenic B cell maturation in Flt3-ligand knockout mice.Immunity, inflammation and disease · 2015Article
- Toll-like receptor 9 and interferon-γ receptor signaling suppress the B-cell fate of uncommitted progenitors in mice.European journal of immunology · 2015Article
- Early B lymphocyte development: Similarities and differences in human and mouse.World journal of stem cells · 2014Review
- Developmental gene networks: a triathlon on the course to T cell identity.Nature reviews. Immunology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hoxa9 and Flt3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow. Mice deficient for Hoxa9, Flt3, or Flt3 ligand (FL) have reduced numbers of lymphoid-primed multipotential progenitors (LMPP), common lymphoid progenitors (CLP), and B/T cell precursors. Hoxa9 regulates lymphoid development, in part, through transcriptional regulation of Flt3. However, it was unclear whether Hoxa9 has functions in lymphopoiesis independent of, or alternatively, synergistically with Flt3 signaling. In this study, we show that Hoxa9(-/-)Flt3l(-/-) mice have more severe deficiencies in all B lineage cells, CLP, LMPP, and total Flt3(+) MPP in bone marrow than the single knockouts. Although LMPP and Flt3(+) CLP contain precursors for NK and dendritic cell lineage cells, no deficiencies in these lineages beyond that in Flt3l(-/-) mice was found. Thymocyte cellularity was significantly reduced in the compound knockout, although peripheral T cell numbers mirrored Flt3l(-/-) mice. Analysis of the hematopoietic progenitor compartment revealed elevated numbers of CD150(+hi)CD34(-)CD41(+) myeloid-biased stem cells in Hoxa9(-/-)Flt3l(-/-) mice. In contrast, CD150(-) MPP enriched for lymphoid potential were synergistically reduced, suggesting Hoxa9 and Flt3 signaling function coordinately to regulate lymphopoiesis at a very early stage. Real-time PCR analysis of CD150(-)Flt3(+) cells from wild-type control, Hoxa9(-/-), and Flt3l(-/-) single knockouts revealed decreased lymphoid transcripts, corroborating the importance of these regulators in lymphoid development. Taken together, these studies reveal a very early checkpoint in lymphopoiesis dependent on the combinatorial activities of Hoxa9 function and Flt3 signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.