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Related Concept Videos

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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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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Maintenance of the ES Cell State01:14

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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Commitment is the  process whereby stem cells:
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Hematopoiesis01:21

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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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Regulation of Hematopoietic Stem Cells01:01

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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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Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program.

Longfei Gao1, Heather Lee1, Joshua H Goodman1

  • 1Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.

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Stem cell niche formation and maintenance rely on different molecular processes. Understanding these distinct mechanisms in mesenchymal stromal cells (MSCs) could advance regenerative medicine.

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Developmental biology

Background:

  • The stem cell niche, crucial for stem cell function, is often viewed as a static structure.
  • The molecular regulation governing the initial formation versus ongoing maintenance of stem cell niches is poorly understood.
  • Mesenchymal stromal cells (MSCs) are key constituents of the hematopoietic stem cell (HSC) niche.

Purpose of the Study:

  • To investigate whether distinct molecular mechanisms regulate the establishment and maintenance of the HSC niche.
  • To compare the roles of m6A mRNA methylation in perinatal versus adult MSCs within the HSC niche.

Main Methods:

  • Comparative analysis of perinatal and adult bone marrow MSCs.
  • Investigated the expression and function of Mettl3 (an m6A methyltransferase) and its target Klf2 in MSCs.
  • Utilized genetic deletion strategies (Mettl3, Klf2) in developing and adult MSCs and osteoblasts.
  • Assessed HSC niche formation and osteogenic differentiation.

Main Results:

  • Perinatal MSCs show enrichment in genes related to m6A mRNA methylation, with Mettl3 expression downregulated post-birth.
  • Mettl3 deletion in developing MSCs impairs HSC niche formation and promotes osteogenic differentiation.
  • Klf2 deletion rescues the HSC niche defect caused by Mettl3 deletion in developing MSCs.
  • Mettl3 deletion in postnatal MSCs does not impact the HSC niche.

Conclusions:

  • Stem cell niche generation and maintenance are controlled by distinct molecular mechanisms.
  • m6A mRNA methylation, specifically Mettl3 activity in developing MSCs, is critical for HSC niche establishment.
  • These findings offer potential targets for regenerative medicine strategies aimed at modulating stem cell niches.