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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 Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Multipotency of Hematopoietic Stem Cells01:19

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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Differentiation of Common Myeloid Progenitor Cells01:15

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Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
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Hematopoiesis01:21

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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Stem Cell Niche01:26

Stem Cell Niche

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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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Differential requirements for Smarca5 expression during hematopoietic stem cell commitment.

Tereza Turkova1, Juraj Kokavec1, Tomas Zikmund1

  • 1Hematology Laboratories, BIOCEV; 1st Faculty of Medicine, Charles University, Vestec, Czech Republic.

Communications Biology
|February 29, 2024
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Summary
This summary is machine-generated.

The SWI/SNF ATPase SMARCA5 (SNF2H) is crucial for hematopoietic cell development. A hypomorphic allele rescues developmental defects and reveals SMARCA5

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Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • Chromatin Remodeling

Background:

  • Hematopoietic cell formation depends on ISWI ATPase SMARCA5 (SNF2H) chromatin remodeling complexes.
  • Smarca5 null and conditional mouse models show varied phenotypes, from embryonic lethality to less severe organ-specific defects.

Purpose of the Study:

  • To investigate the function of SMARCA5 in hematopoiesis using a hypomorphic allele (S5tg).
  • To determine the impact of SMARCA5 gene dosage on embryonic development and hematopoietic stem cell differentiation.

Main Methods:

  • Utilized Smarca5 hypomorphic (S5tg) and knockout mouse models.
  • Employed Cre-lox systems (hCD2iCre, Vav1iCre) for tissue-specific gene deletion.
  • Analyzed hematopoietic stem and progenitor cell populations and differentiation potential.

Main Results:

  • The S5tg allele rescued developmental arrest in hematopoiesis and lethal phenotypes in knockout models.
  • Vav1iCre-driven S5tg mice showed accumulation of hematopoietic stem and progenitor cells.
  • Impaired lymphoid lineage entry and differentiation were observed in these cells, contrasting with normal myeloid development.

Conclusions:

  • SMARCA5 gene dosage influences hematopoietic stem cell function and lymphoid differentiation.
  • Low SMARCA5 expression permits normal embryonic development but alters lymphoid entry within hematopoietic stem cells.