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Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil

  • Role of Classical Signaling Pathways in Stem Cell Maintenance (A Cardoso and N Carlesso, Section Editors)
  • Published:
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Abstract

Purpose of Review

This review summarizes the role of hypoxia and hypoxia-inducible factors (HIFs) in the regulation of stem cell biology, specifically focusing on maintenance, differentiation, and stress responses in the context of several stem cell systems. Stem cells for different lineages/tissues reside in distinct niches, and are exposed to diverse oxygen concentrations. Recent studies have revealed the importance of the hypoxia signaling pathway for stem cell functions.

Recent Findings

Hypoxia and HIFs contribute to maintenance of embryonic stem cells, generation of induced pluripotent stem cells, functionality of hematopoietic stem cells, and survival of leukemia stem cells. Harvest and collection of mouse bone marrow and human cord blood cells in ambient air results in fewer hematopoietic stem cells recovered due to the phenomenon of Extra PHysiologic Oxygen Shock/Stress (EPHOSS).

Summary

Oxygen is an important factor in the stem cell microenvironment. Hypoxia signaling and HIFs play important roles in modeling cellular metabolism in both stem cells and niches to regulate stem cell biology, and represent an additional dimension that allows stem cells to maintain an undifferentiated status and multilineage differentiation potential.

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Acknowledgements

We thank other members in the Broxmeyer laboratory for helpful discussion and assistance. This work is supported by US Public Health Service Grants from the NIH to HEB: (R01 HL112669, R01 HL056416, U54 DK106846). AA is supported by NIH 5T32DK007519-32 to HEB, and TT is supported by NIH T32DK064466.

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  1. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Xinxin Huang, Thao Trinh, Arafat Aljoufi & Hal E. Broxmeyer

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  1. Xinxin Huang
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  2. Thao Trinh
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Correspondence to Xinxin Huang.

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Xinxin Huang, Thao Trinh, and Arafat Aljoufi declare that they have no conflict of interest. Dr. Broxmeyer is a member of the Medical Scientific Advisory Board of CordUse, a cord blood banking company based in Orlando, Florida, but he reports no financial support.

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This article is part of the Topical Collection on Role of Classical Signaling Pathways in Stem Cell Maintenance

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Huang, X., Trinh, T., Aljoufi, A. et al. Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil. Curr Stem Cell Rep 4, 149–157 (2018). https://doi.org/10.1007/s40778-018-0127-7

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