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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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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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Lineage Commitment

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Commitment is the  process whereby stem cells:
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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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Abnormal Proliferation02:23

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis
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Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2.

Sarah A Kinkel1, Roman Galeev2, Christoffer Flensburg3

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia;

Blood
|February 4, 2015
PubMed
Summary
This summary is machine-generated.

Jarid2 is crucial for Polycomb repressive complex 2 (PRC2) function in hematopoietic stem and progenitor cells (HSPCs). Depleting Jarid2 enhances HSPC transplantation and expansion capabilities, highlighting its role in coordinating cell function.

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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Area of Science:

  • Epigenetics and Gene Regulation
  • Hematopoiesis
  • Stem Cell Biology

Background:

  • Polycomb repressive complex 2 (PRC2) is vital for hematopoietic stem and progenitor cell (HSPC) function.
  • The precise targeting mechanisms of PRC2 in HSPCs remain largely unknown.

Purpose of the Study:

  • To investigate the role of PRC2 accessory factors in HSPC function.
  • To determine the function of Jarid2 in regulating HSPC behavior.

Main Methods:

  • Short hairpin RNA-mediated knockdown of PRC2 accessory factors in murine HSPCs.
  • Competitive transplantation assays to assess HSPC function.
  • Gene expression profiling to identify target genes.

Main Results:

  • Depletion of Jarid2, similar to Suz12, enhances the competitive transplantation capacity of fetal and adult mouse HSPCs.
  • JARID2 depletion improves in vitro expansion and in vivo reconstitution of human HSPCs.
  • Common target genes of Suz12 and Jarid2 are enriched for the H3K27me3 mark.

Conclusions:

  • Jarid2 is an important component of PRC2 that plays a central role in coordinating HSPC function.
  • Targeting Jarid2 can enhance HSPC regenerative potential.