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Related Concept Videos

Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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...
Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Hematopoiesis01:21

Hematopoiesis

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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Related Experiment Video

Updated: May 30, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
12:04

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

The Paf oncogene is essential for hematopoietic stem cell function and development.

Yacine M Amrani1, Jonathan Gill, Armine Matevossian

  • 1Immunology Program, Sloan-Kettering Institute, 3 Department of Pediatrics, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

The Journal of Experimental Medicine
|August 17, 2011
PubMed
Summary
This summary is machine-generated.

Proliferating cell nuclear antigen-associated factor (Paf) is essential for hematopoietic stem cells (HSCs) to produce blood cells. Mice lacking Paf show impaired blood production and reduced HSCs due to increased apoptosis and reactive oxygen species.

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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

Area of Science:

  • Hematology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Hematopoietic stem cells (HSCs) are crucial for lifelong blood cell production.
  • Self-renewal of HSCs maintains hematopoietic stem cell pools.
  • Understanding HSC regulation is vital for treating blood disorders.

Purpose of the Study:

  • To investigate the role of proliferating cell nuclear antigen-associated factor (Paf) in hematopoiesis.
  • To elucidate the mechanisms by which Paf regulates hematopoietic stem cell function.
  • To identify Paf as a potential therapeutic target in hematopoietic disorders.

Main Methods:

  • Generation and analysis of Paf-deficient mouse models.
  • Flow cytometry to assess hematopoietic stem and progenitor cell populations.
  • Measurement of reactive oxygen species (ROS) levels in HSCs.
  • Assessment of apoptosis via p53-mediated pathways.
  • Treatment with N-acetylcysteine to evaluate the role of ROS.

Main Results:

  • Paf deficiency leads to reduced bone marrow cellularity, HSCs, and progenitors, causing leukopenia.
  • Paf loss causes intrinsic developmental blockage of long-term HSCs and lymphoid progenitor loss via p53-mediated apoptosis.
  • Paf-deficient HSCs exhibit increased ROS, impaired quiescence, and reduced hematopoietic support.
  • Antioxidant treatment with N-acetylcysteine rescues lymphoid progenitor numbers in Paf-deficient mice.

Conclusions:

  • Paf is a novel and essential regulator of early hematopoiesis.
  • Paf controls HSC development and survival by modulating ROS levels and apoptosis.
  • Targeting Paf may offer new strategies for managing hematopoietic disorders.