Defining the Role of Oxygen Tension in Human Neural Progenitor Fate
Hypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114003063 |
| _version_ | 1818353125735530496 |
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| author | Yuan Xie Jin Zhang Ying Lin Xavier Gaeta Xiangzhi Meng Dona R.R. Wisidagama Jessica Cinkornpumin Carla M. Koehler Cindy S. Malone Michael A. Teitell William E. Lowry |
| author_facet | Yuan Xie Jin Zhang Ying Lin Xavier Gaeta Xiangzhi Meng Dona R.R. Wisidagama Jessica Cinkornpumin Carla M. Koehler Cindy S. Malone Michael A. Teitell William E. Lowry |
| author_sort | Yuan Xie |
| collection | DOAJ |
| description | Hypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and hypoxia-inducible factor (HIF) activity instead promote appropriate hESC differentiation. Through gain- and loss-of-function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate toward neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types. |
| first_indexed | 2024-12-13T19:04:34Z |
| format | Article |
| id | doaj.art-f150f12417194f82aa00d733a5ab8722 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-13T19:04:34Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-f150f12417194f82aa00d733a5ab87222022-12-21T23:34:36ZengElsevierStem Cell Reports2213-67112014-11-013574375710.1016/j.stemcr.2014.09.021Defining the Role of Oxygen Tension in Human Neural Progenitor FateYuan Xie0Jin Zhang1Ying Lin2Xavier Gaeta3Xiangzhi Meng4Dona R.R. Wisidagama5Jessica Cinkornpumin6Carla M. Koehler7Cindy S. Malone8Michael A. Teitell9William E. Lowry10Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Biology, California State University, Northridge, Northridge, CA 91330, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Biology, California State University, Northridge, Northridge, CA 91330, USAEli and Edythe Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USAHypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and hypoxia-inducible factor (HIF) activity instead promote appropriate hESC differentiation. Through gain- and loss-of-function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate toward neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types.http://www.sciencedirect.com/science/article/pii/S2213671114003063 |
| spellingShingle | Yuan Xie Jin Zhang Ying Lin Xavier Gaeta Xiangzhi Meng Dona R.R. Wisidagama Jessica Cinkornpumin Carla M. Koehler Cindy S. Malone Michael A. Teitell William E. Lowry Defining the Role of Oxygen Tension in Human Neural Progenitor Fate Stem Cell Reports |
| title | Defining the Role of Oxygen Tension in Human Neural Progenitor Fate |
| title_full | Defining the Role of Oxygen Tension in Human Neural Progenitor Fate |
| title_fullStr | Defining the Role of Oxygen Tension in Human Neural Progenitor Fate |
| title_full_unstemmed | Defining the Role of Oxygen Tension in Human Neural Progenitor Fate |
| title_short | Defining the Role of Oxygen Tension in Human Neural Progenitor Fate |
| title_sort | defining the role of oxygen tension in human neural progenitor fate |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114003063 |
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