Evidence map›Paper›PMID 24444745›Full record

ArticleExperimental hematology2014

Flt3 signaling regulates the proliferation, survival, and maintenance of multipotent hematopoietic progenitors that generate B cell precursors.

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

Abstract read
In one paragraph

Article in Experimental hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Ex Vivo Expansion and Homing of Human Cord Blood Hematopoietic Stem Cells.Advances in experimental medicine and biology · 2023
    Article
  6. Flt3 Signaling in B Lymphocyte Development and Humoral Immunity.International journal of molecular sciences · 2022
    Review
  7. Article
  8. The Cytokine Flt3-Ligand in Normal and Malignant Hematopoiesis.International journal of molecular sciences · 2017
    Review
  9. Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  10. Article
  11. Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Joseph J DolenceDepartment of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA; Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA.
Kimberly A GwinDepartment of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Mariya B ShapiroDepartment of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Kay L MedinaDepartment of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA; Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: medina.kay@mayo.edu.
Mayo Clinic · US

Funding

PHD TRAINING PROGRAM IN BASIC IMMUNOLOGYT32AI007425 · NIAID · MAYO CLINIC ROCHESTER · PI SHAPIRO, VIRGINIA SMITH · 1995 to 2020
$3.6M
TRAINING PROGRAM IN ALLERGIC DISEASEST32AI007047 · NIAID · MAYO CLINIC ROCHESTER · PI KITA, HIROHITO · 1985 to 2016
$2.0M
Molecular Events Initiating B Cell Fate DeterminationR01HL096108 · NHLBI · MAYO CLINIC ROCHESTER · PI MEDINA, KAY LYNN · 2009 to 2013
$1.9M
NHLBI NIH HHS R01 HL096108NHLBI NIH HHS R01HL096108NIAID NIH HHS T32 AI007047NIAID NIH HHS T32 AI007425NIAID NIH HHS T32AI07425
6 · The paper itself

Abstract

Flt3 signaling plays a crucial role in regulating the survival and differentiation of lymphoid progenitors into B cell precursors (BCPs) in bone marrow. To define further the role of Flt3 signaling in lymphoid progenitor survival, mice deficient in Flt3 ligand that also expressed a Bcl2 transgene (Eμ-bcl2tg flt3l(-/-)) were generated. Intracellular flow cytometry established transgene expression in primitive hematopoietic progenitors, including lineage-negative Sca-1(+) c-kit(+) (LSK(+)) CD27(-) cells enriched for functional hematopoietic stem cells. Compared with flt3l(-/-) mice, Eμ-bcl2tg flt3l(-/-) mice had significantly increased multipotential progenitors (MPPs), IL-7R(+) common lymphoid progenitors, and B cell precursors. To determine whether forced expression of Bcl2 was sufficient to restore lymphoid priming in the absence of Flt3 signaling Eμ-bcl2tg flt3l(-/-)rag1-gfp(+) mice were generated. Analysis of Eμ-bcl2tg flt3l(-/-)rag1-gfp(+) mice revealed that the Bcl2 transgene had no effect on lymphoid priming before CD19 expression. Thus, forced expression of a survival gene can bypass the requirement for threshold levels of Flt3 signaling requisite for lymphoid priming. Temporal Flt3 ligand (FL) replacement therapy in flt3l(-/-) mice revealed specific requirements for Flt3 signaling in the expansion and maintenance of Flt3(+hi) MPP and Flt3(+) all lymphoid progenitors, but not Flt3(+) B lymphoid progenitors (BLPs), the immediate precursors of BCPs. BCPs were restored after temporal in vivo FL treatment, albeit with delayed kinetics. Together, these results show that Flt3 regulates the proliferation, survival, and maintenance of developmental stage-specific hematopoietic progenitors that give rise to BCPs.

Indexed as

Cell ProliferationAnimalsCell Survivalfms-Like Tyrosine Kinase 3MiceMice, KnockoutMultipotent Stem CellsPrecursor Cells, B-LymphoidProto-Oncogene Proteins c-bcl-2TransgenesBcl2 protein, mouseFlt3 protein, mousefms-Like Tyrosine Kinase 3Proto-Oncogene Proteins c-bcl-2

Identifiers

PMID24444745
PMCPMC4089881
OpenAlexW2002549951

What OpenQuestion holds

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Registered trials

None linked

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.