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Related Concept Videos

Embryonic Stem Cells00:58

Embryonic Stem Cells

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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Embryonic Stem Cells00:57

Embryonic Stem Cells

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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
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Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.2K
Tissue Renewal without Stem Cells01:23

Tissue Renewal without Stem Cells

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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...
2.1K
Renewal of Skin Epidermal Stem Cells01:12

Renewal of Skin Epidermal Stem Cells

3.0K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
3.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Derivation of Hematopoietic Stem Cells from Murine Embryonic Stem Cells
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Derivation of Hematopoietic Stem Cells from Murine Embryonic Stem Cells

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Genomic Integrity Safeguards Self-Renewal in Embryonic Stem Cells.

Jie Su1, Dandan Zhu2, Zijun Huo3

  • 1Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Cell Reports
|August 8, 2019
PubMed
Summary

Maintaining embryonic stem cell (ESC) self-renewal requires genomic integrity. Disrupting phosphoregulators or genome integrity genes activates p53, leading to ESC differentiation and loss of pluripotency.

Keywords:
DNA damageembryonic stem cellgenomic instabilitylineage differentationp53self-renewal

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Derivation of Human Embryonic Stem Cells by Immunosurgery
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Profiling Individual Human Embryonic Stem Cells by Quantitative RT-PCR
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Profiling Individual Human Embryonic Stem Cells by Quantitative RT-PCR

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Profiling Individual Human Embryonic Stem Cells by Quantitative RT-PCR
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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Embryonic stem cells (ESCs) possess self-renewal capacity, crucial for development.
  • Maintaining the ESC state involves complex internal and external signaling networks.
  • Pluripotency-associated phosphoregulators (PRs) are key regulators of ESC self-renewal.

Purpose of the Study:

  • To identify essential phosphoregulators (PRs) maintaining ESC self-renewal.
  • To investigate the molecular mechanisms linking PRs to ESC fate.
  • To establish the role of genomic integrity in ESC self-renewal and differentiation.

Main Methods:

  • Short hairpin RNA (shRNA) screening to identify PRs.
  • Global gene expression profiling.
  • Computational analyses to assess signaling pathways.
  • p53 activity assays.

Main Results:

  • Depletion of 5 PRs (Aurka, Bub1b, Chek1, Ppm1g, Ppp2r1b) compromises ESC self-renewal and induces differentiation.
  • Knockdown of these PRs leads to DNA damage and genome instability.
  • This instability activates the p53 pathway, resulting in ESC differentiation.
  • Disruption of genome integrity genes also compromises ESC self-renewal via p53 activation.

Conclusions:

  • Genomic integrity is essential for maintaining ESC self-renewal.
  • The p53 pathway acts as a critical mediator between genome stability and ESC fate.
  • Phosphoregulators play a vital role in safeguarding genomic integrity in ESCs.