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Related Concept Videos

Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Lineage Commitment

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Commitment is the  process whereby stem cells:
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Hematopoiesis

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The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
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Multipotency of Hematopoietic Stem Cells

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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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Overview of Hematopoiesis01:20

Overview of Hematopoiesis

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Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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WBP1L regulates hematopoietic stem cell function and T cell development.

Imtissal Krayem1, Srdjan Grusanovic2, Iris Duric1,3

  • 1Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.

Frontiers in Immunology
|November 18, 2024
PubMed
Summary

WW domain binding protein 1-like (WBP1L) regulates hematopoietic stem cell function and leukocyte production. Its absence in mice leads to dysregulated hematopoiesis, enlarged thymi, and altered blood cell counts.

Keywords:
T cell developmentWBP1Lhematopoiesishematopoietic stem and progenitor cell transplantationhematopoietic stem cellstransmembrane adaptor protein

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Phenotypic Analysis and Isolation of Murine Hematopoietic Stem Cells and Lineage-committed Progenitors
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Area of Science:

  • Hematology
  • Immunology
  • Molecular Biology

Background:

  • WW domain binding protein 1-like (WBP1L), also known as outcome predictor of acute leukemia 1 (OPAL1), is a transmembrane adaptor protein.
  • WBP1L expression correlates with ETV6-RUNX1 translocation and favorable prognosis in childhood leukemia.
  • Previous studies identified WBP1L as a regulator of CXCR4 signaling and hematopoiesis.

Purpose of the Study:

  • To investigate the role of WBP1L in regulating hematopoiesis and immune cell populations.
  • To determine the effects of WBP1L deficiency on hematopoietic stem cells (HSCs) and progenitor cells.
  • To analyze the impact of WBP1L on thymic development and leukocyte homeostasis.

Main Methods:

  • Germline deletion of Wbp1l in mice.
  • Analysis of hematopoietic stem cell and progenitor cell populations.
  • Flow cytometry to assess thymocyte and peripheral blood cell subsets.
  • Hematopoietic stem and progenitor cell transplantation experiments.

Main Results:

  • Wbp1l germline deletion results in dysregulated hematopoiesis at the HSC and early progenitor levels.
  • WBP1L-deficient mice exhibit significantly enlarged thymi with increased thymocyte numbers across all subsets.
  • Increased generation of multipotent progenitors 4 (MPP4) in bone marrow and elevated leukocyte counts in blood were observed.
  • WBP1L regulates HSC functionality and leukocyte progenitor proliferation, leading to enhanced engraftment of WBP1L-deficient cells post-transplantation.

Conclusions:

  • WBP1L is a critical regulator of hematopoietic stem and progenitor cell function.
  • WBP1L controls leukocyte numbers in both steady-state conditions and after bone marrow transplantation.
  • Dysregulation of WBP1L impacts thymic development and peripheral blood cell homeostasis.