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Related Concept Videos

Multipotency of Hematopoietic Stem Cells01:19

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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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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 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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YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance.

Hongna Zuo1,2, Jin Liu1,2, Bin Shen3

  • 1Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Cell Death Discovery
|October 16, 2024
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The nuclear protein YTHDC1 is crucial for maintaining hematopoietic stem cell (HSC) function and self-renewal by regulating microRNA maturation. Its absence leads to HSC loss, highlighting the YTHDC1-HP1BP3-microRNA axis

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Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • RNA Biology

Background:

  • N6-methyladenosine (m6A) modifications regulate RNA metabolism.
  • YTHDC1 is an m6A reader protein.
  • The role of YTHDC1 in hematopoietic stem cell (HSC) homeostasis is not fully understood.

Purpose of the Study:

  • Investigate the function of YTHDC1 in normal hematopoiesis and HSC maintenance.
  • Elucidate the mechanisms by which YTHDC1 regulates HSCs.

Main Methods:

  • Utilized conditional Ythdc1 knockout mice and Ythdc1/Mettl3 double knockout mice.
  • Analyzed HSC maintenance, self-renewal, and apoptosis.
  • Examined microRNA maturation and levels.
  • Investigated protein interactions, specifically YTHDC1 with HP1BP3.

Main Results:

  • YTHDC1 is essential for HSC maintenance and self-renewal in vivo.
  • YTHDC1 deficiency leads to HSC apoptosis and altered microRNA levels.
  • YTHDC1 interacts with HP1BP3, a nuclear RNA binding protein involved in microRNA maturation.
  • Overexpression of specific microRNAs partially rescued YTHDC1-null HSC defects.

Conclusions:

  • The YTHDC1-HP1BP3-microRNA maturation axis is vital for long-term HSC maintenance.
  • YTHDC1 plays a critical role in regulating hematopoiesis through microRNA pathways.