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Epigenetic Regulation01:46

Epigenetic Regulation

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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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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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.
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The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
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Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development.

Dionna M Kasper1, Stefania Nicoli1,2,3

  • 1Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06511, USA.

Current Stem Cell Reports
|June 19, 2018
PubMed
Summary

Epigenetic and epitranscriptomic factors are crucial for transforming endothelial cells into hematopoietic stem cells. These molecular mechanisms dynamically regulate gene expression during this critical blood development process.

Keywords:
HSC productionchromatin modificationendothelial to hematopoietic transitionhemogenic endotheliumm6A methylationtransdifferentiation

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Blood specification involves the transdifferentiation of hemogenic endothelial cells (ECs) into hematopoietic stem cells (HSCs).
  • Significant gene expression changes are necessary for this cell identity switch.
  • The factors mediating endothelial to hematopoietic reprogramming were largely unknown.

Purpose of the Study:

  • To review the higher-order mechanisms driving endothelial to hematopoietic reprogramming.
  • To summarize identified factors involved in this cell fate transition.

Main Methods:

  • Review of accumulating evidence from mouse and zebrafish studies.
  • Analysis of chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors.

Main Results:

  • Epigenetic and epitranscriptomic factors are essential for HSC formation from hemogenic endothelium.
  • These factors operate throughout the endothelial-hematopoietic transition.
  • A dynamic interplay between epigenetic and epitranscriptomic machineries is suggested.

Conclusions:

  • Epigenetic and epitranscriptomic regulation are key to reshaping EC gene expression for HSC production.
  • Understanding these modification dynamics is vital for elucidating the molecular mechanisms of HSC development from hemogenic endothelium.