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Related Concept Videos

Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

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...
Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

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A Culture Method to Maintain Quiescent Human Hematopoietic Stem Cells
07:14

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Published on: May 17, 2021

p53 regulates hematopoietic stem cell quiescence.

Yan Liu1, Shannon E Elf, Yasuhiko Miyata

  • 1Molecular Phamacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Cell Stem Cell
|January 9, 2009
PubMed
Summary

The p53 protein is crucial for maintaining quiescent hematopoietic stem cells (HSCs) during normal blood formation. Understanding its role and target genes could aid in developing therapies against quiescent cancer stem cells.

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Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Hematopoiesis

Background:

  • The role of p53 protein in DNA damage response is established.
  • Its function in steady-state hematopoiesis remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of p53 in regulating hematopoietic stem cell (HSC) quiescence.
  • To identify p53 target genes involved in HSC cell-cycle control.

Main Methods:

  • Utilized transcription profiling of HSCs from wild-type and p53 null mice.
  • Employed lentiviral vectors for gene expression manipulation (upregulation/knockdown).
  • Assessed the impact of gene modulation on HSC quiescence.

Main Results:

  • Identified Gfi-1 and Necdin as direct p53 target genes in HSCs.
  • Demonstrated the critical role of Gfi-1 and Necdin in regulating HSC quiescence.
  • Showed that p53 promotes enhanced quiescence in HSCs, particularly when MEF/ELF4 is absent.

Conclusions:

  • p53 plays a vital role in maintaining hematopoietic stem cell quiescence.
  • p53 target genes, Gfi-1 and Necdin, are key regulators of HSC cell-cycle entry.
  • Findings may inform therapeutic strategies targeting quiescent cancer stem cells.