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Related Concept Videos

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...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Stem Cell Niche01:26

Stem Cell Niche

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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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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.
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Regulation of Angiogenesis and Blood Supply

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Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
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O2 regulates stem cells through Wnt/β-catenin signalling.

Jolly Mazumdar1, W Timothy O'Brien, Randall S Johnson

  • 1Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Nature Cell Biology
|September 21, 2010
PubMed
Summary

Oxygen levels regulate stem cell function. Hypoxia inducible factor-1α (HIF-1α) enhances Wnt/β-catenin signaling in stem cells, crucial for neural stem cell proliferation and differentiation in the brain.

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Last Updated: Jun 8, 2026

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
10:05

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Published on: May 8, 2020

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Affordable Oxygen Microscopy-Assisted Biofabrication of Multicellular Spheroids

Published on: April 6, 2022

Area of Science:

  • Stem cell biology
  • Neuroscience
  • Molecular biology

Background:

  • Stem cells are regulated by their microenvironment (niches).
  • Hypoxic conditions (low oxygen) in vitro strongly influence stem and precursor cell functions.
  • Mechanisms linking oxygen availability to stem cell regulation are not fully understood.

Purpose of the Study:

  • To investigate the role of hypoxia inducible factor-1α (HIF-1α) in modulating stem cell signaling under hypoxic conditions.
  • To determine if HIF-1α affects Wnt/β-catenin signaling in embryonic stem cells and neural stem cells.
  • To examine the in vivo relevance of HIF-1α and Wnt/β-catenin signaling in neural stem cell niches.

Main Methods:

  • Utilized in vitro hypoxic culture conditions (<5% O2).
  • Assessed Wnt/β-catenin signaling activation and downstream gene expression (LEF-1, TCF-1) in embryonic stem cells and neural stem cells.
  • Investigated Hif-1α deletion effects on neural stem cell (NSC) proliferation, differentiation, and neuronal maturation in vivo within the hippocampus.

Main Results:

  • Hypoxia inducible factor-1α (HIF-1α) enhances Wnt/β-catenin signaling activation in hypoxic embryonic stem cells.
  • This HIF-1α-mediated regulation of Wnt/β-catenin signaling was observed in primary neural stem cells but not in differentiated cells.
  • In vivo, Wnt/β-catenin activity correlated with low oxygen regions in the hippocampal subgranular zone, a key NSC niche.
  • Hif-1α deletion in vivo impaired hippocampal NSC proliferation, differentiation, and neuronal maturation, linked to reduced Wnt/β-catenin signaling.

Conclusions:

  • Oxygen availability directly influences stem cell regulation.
  • HIF-1α plays a critical role in modulating Wnt/β-catenin signaling in response to hypoxia.
  • This pathway is essential for maintaining neural stem cell function and neurogenesis within the hippocampal niche.