Defining the role of oxygen tension in human neural progenitor fate
Open accessAbstract
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.
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Exposure of NPCs to hypoxia, which boosts aerobic glycolysis, leads to more glial cells during neuronal differentiation.
“it has been reported that exposure of NPCs to hypoxia, which boosts aerobic glycolysis, leads to more glial cells during neuronal differentiation (Xie et al., 2014).”
From Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation (2016) · cites this paper as Xie et al., 2014
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Cites
Embryonic Stem Cell Lines Derived from Human Blastocysts
Thomson, J. A., Itskovitz‐Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,947 · see citing works
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,820 · see citing works
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Hypoxia, HIF1 and glucose metabolism in the solid tumour
Denko, N. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2468 · Cited by 1,707 · see citing works
Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones‐Hinojosa, A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.07.007 · Cited by 1,536 · see citing works
Targeting MYC dependence in cancer by inhibiting BET bromodomains
Mertz, J. A., Conery, A. R., Bryant, B. M., Sandy, P., Balasubramanian, S., Mele, D. A., Bergeron, L., & Sims, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108190108 · Cited by 1,118 · see citing works
Generation of human induced pluripotent stem cells from dermal fibroblasts
Lowry, W. E., Richter, L., Yachechko, R., Pyle, A. D., Tchieu, J., Sridharan, R., Clark, A. T., & Plath, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711983105 · Cited by 1,041 · see citing works
Self-citationThe role of oxygen availability in embryonic development and stem cell function
Simon, M. C., & Keith, B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2354 · Cited by 966 · see citing works
Hypoxia signalling through mTOR and the unfolded protein response in cancer
Wouters, B. G., & Koritzinsky, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2501 · Cited by 894 · see citing works
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885 · see citing works
Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C., Labosky, P. A., Simon, M. C., & Keith, B. (2006) · Genes & Development · doi:10.1101/gad.1399906 · Cited by 818 · see citing works
Low O 2 tensions and the prevention of differentiation of hES cells
Ezashi, T., Das, P., & Roberts, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501283102 · Cited by 804 · see citing works
HIF-2α Promotes Hypoxic Cell Proliferation by Enhancing c-Myc Transcriptional Activity
Gordan, J. D., Bertout, J. A., Hu, C.-J., Diehl, J. A., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.006 · Cited by 781 · see citing works
Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells
Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T., & Yamanaka, S. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.08.001 · Cited by 757 · see citing works
HIF-1α induces cell cycle arrest by functionally counteracting Myc
Koshiji, M., Kageyama, Y., Pete, E. A., Horikawa, I., Barrett, J. C., & Huang, L. E. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600196 · Cited by 652 · see citing works
The Role of Hypoxia in Development of the Mammalian Embryo
Dunwoodie, S. L. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.11.008 · Cited by 651 · see citing works
Xia, X., Lemieux, M. E., Li, W., Carroll, J. S., Brown, M., Liu, X. S., & Kung, A. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810067106 · Cited by 410 · see citing works
Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation
Chang, T.-C., Zeitels, L. R., Hwang, H., Chivukula, R. R., Wentzel, E. A., Dews, M., Jung, J. J., Gao, P., Dang, C. V., Beer, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808300106 · Cited by 403 · see citing works
Lengner, C. J., Gimelbrant, A. A., Erwin, J. A., Cheng, A. W., Guenther, M. G., Welstead, G. G., Alagappan, R. K., Frampton, G. M., Xu, P. A., Muffat, J., et al. (2010) · Cell · doi:10.1016/j.cell.2010.04.010 · Cited by 398 · see citing works
Forristal, C. E., Wright, K. L., Hanley, N. A., Oreffo, R. O. C., & Houghton, F. D. (2009) · Reproduction · doi:10.1530/rep-09-0300 · Cited by 396 · see citing works
Lum, D. H., Kuwabara, P. E., Zarkower, D. A., & Spence, A. M. (2000) · Genes & Development · doi:10.1101/gad.853700 · Cited by 392 · see citing works
Generating specificity and diversity in the transcriptional response to hypoxia
Lendahl, U., Lee, K. L., Yang, H. H., & Poellinger, L. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2665 · Cited by 330 · see citing works
ARNT-Deficient Mice and Placental Differentiation
Kozak, K. R., Abbott, B., & Hankinson, O. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8758 · Cited by 328 · see citing works
Amarilio, R., Viukov, S. V., Sharir, A., Eshkar-Oren, I., Johnson, R. S., & Zelzer, E. (2007) · Development · doi:10.1242/dev.008441 · Cited by 317 · see citing works
Defective Brain Development in Mice Lacking the Hif-1 α Gene in Neural Cells
Tomita, S., Ueno, M., Sakamoto, M., Kitahama, Y., Ueki, M., Nobuhiro Maekawa, A., Sakamoto, H., Gassmann, M., Kageyama, R., Ueda, N., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.19.6739-6749.2003 · Cited by 250 · see citing works
Hypoxia-Inducible Factors 1α and 2α Regulate Trophoblast Differentiation
Dahl, K. D. C., Fryer, B. H., Mack, F. A., Compernolle, V., Maltepe, E., Adelman, D. M., Carmeliet, P., & Simon, M. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10479-10491.2005 · Cited by 228 · see citing works
SOX2–LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors
Cimadamore, F., Amador‐Arjona, A., Chen, C., Huang, C., & Terskikh, A. V. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220176110 · Cited by 216 · see citing works
Conserved microRNA pathway regulates developmental timing of retinal neurogenesis
Torre, A. L., Georgi, S. A., & Reh, T. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301837110 · Cited by 212 · see citing works
Hif-1α regulates differentiation of limb bud mesenchyme and joint development
Provot, S., Zinyk, D. L., Güneş, Y., Kathri, R., Le, Q., Kronenberg, H. M., Johnson, R. S., Longaker, M. T., Giaccia, A. J., & Schipani, E. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612023 · Cited by 199 · see citing works
Drosophila Argonaute1 and Argonaute2 Employ Distinct Mechanisms for Translational Repression
Iwasaki, S., Kawamata, T., & Tomari, Y. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.02.010 · Cited by 193 · see citing works
Balzer, E., Heine, C., Jiang, Q., Lee, V. M., & Moss, E. G. (2010) · Development · doi:10.1242/dev.042895 · Cited by 184 · see citing works
Oxygen and Ion Concentrations in Normoxic and Hypoxic Brain Cells
Silver, I. A., & Erecińska, M. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4863-8_2 · Cited by 161 · see citing works
Defining the nature of human pluripotent stem cell progeny
Patterson, M., Chan, D. N., Ha, I., Case, D., Cui, Y., Handel, B. V., Mikkola, H. K., & Lowry, W. E. (2012) · Cell Research · doi:10.1038/cr.2011.133 · Cited by 145 · see citing works
Krishnan, J., Ahuja, P., Bodenmann, S., Knapik, D., Perriard, E. R., Krek, W., & Perriard, J. (2008) · Circulation Research · doi:10.1161/01.res.0000338613.89841.c1 · Cited by 138 · see citing works
Corn, P. G., Ricci, M., Scata, K. A., Arsham, A. M., Simon, M. C., Dicker, D. T., & El‐Deiry, W. S. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.11.2299 · Cited by 128 · see citing works
Identification of Oxygen-Sensitive Transcriptional Programs in Human Embryonic Stem Cells
Westfall, S. D., Sachdev, S., Das, P., Hearne, L. B., Hannink, M., Roberts, R. M., & Ezashi, T. (2008) · Stem Cells and Development · doi:10.1089/scd.2007.0240 · Cited by 121 · see citing works
Hypoxia Promotes Efficient Differentiation of Human Embryonic Stem Cells to Functional Endothelium
Prado‐Lòpez, S., Conesa, A., Armiñán, A., Martínez‐Losa, M., Escobedo‐Lucea, C., Gandía, C., Tarazona, S., Melguizo‐Sanchis, D., Blesa, D., Montaner, D. A., et al. (2010) · Stem Cells · doi:10.1002/stem.295 · Cited by 115 · see citing works
let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis
Patterson, M., Gaeta, X., Loo, K., Edwards, M., Smale, S., Cinkornpumin, J., Xie, Y., Listgarten, J., Azghadi, S., Douglass, S. M., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.08.015 · Cited by 103 · see citing works
Self-citationSherman, M. H., Kuraishy, A. I., Deshpande, C., Hong, J. S., Cacalano, N. A., Gatti, R. A., Manis, J. P., Damore, M. A., Pellegrini, M. A., & Teitell, M. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.08.019 · Cited by 84 · see citing works
Self-citationKawahara, H., Okada, Y., Imai, T., Iwanami, A., Mischel, P. S., & Okano, H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.199166 · Cited by 81 · see citing works
Mechanisms that regulate the number of neurons during mouse neocortical development
Miyata, T., Kawaguchi, D., Kawaguchi, A., & Gotoh, Y. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.01.001 · Cited by 78 · see citing works
Licht, A. H., Müller-Holtkamp, F., Flamme, I., & Breier, G. (2005) · Blood · doi:10.1182/blood-2005-07-3033 · Cited by 78 · see citing works
Nagao, M., Campbell, K., Burns, K. A., Kuan, C.-Y., Trumpp, A., & Nakafuku, M. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200807130 · Cited by 74 · see citing works
Mutoh, T., Sanosaka, T., Ito, K., & Nakashima, K. (2011) · Stem Cells · doi:10.1002/stem.1019 · Cited by 49 · see citing works
Exogenous expression of HIF-1α promotes cardiac differentiation of embryonic stem cells
Ng, K., Lee, Y.-K., Chan, Y.-C., Lai, W., Fung, M., Li, R. A., Siu, C., & Tse, H. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.01.015 · Cited by 46 · see citing works
Lim, H., Han, J., Woo, D., Kim, S. E., Kim, S., Kang, H., & Kim, J. (2011) · Molecules and Cells · doi:10.1007/s10059-011-0016-8 · Cited by 38 · see citing works
Sanosaka, T., Namihira, M., Asano, H., Kohyama, J., Aisaki, K., Igarashi, K., Kanno, J., & Nakashima, K. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.06.039 · Cited by 36 · see citing works
Yoon, D., Okhotin, D., Kim, B., Okhotina, Y., Okhotin, D. J., Miasnikova, G., Sergueeva, A., Polyakova, L. A., Maslow, A., Lee, Y., et al. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0599-0 · Cited by 17 · see citing works
Ptk7 Marks the First Human Developmental EMT In Vitro
Chan, D. N., Azghadi, S. F., Feng, J., & Lowry, W. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050432 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Adelman D.M. Gertsenstein M. Nagy A. Simon M.C. Maltepe E. Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses Genes Dev. 14 2000 3191 3203 11124810 PMC317149
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Zheng, X., Boyer, L., Jin, M., Mertens, J., Kim, Y., Ma, L., Ma, L., Hamm, M., Gage, F. H., & Hunter, T. (2016) · eLife · doi:10.7554/elife.13374 · Cited by 671 · see citing works
“Interestingly, it has been reported that exposure of NPCs to hypoxia, which boosts aerobic glycolysis, leads to more glial cells during neuronal differentiation (Xie et al., 2014).”
BackgroundKeeley, T. P., & Mann, G. E. (2019) · Physiological Reviews · doi:10.1152/physrev.00041.2017 · Cited by 329 · see citing works
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TeSlaa, T., Chaikovsky, A. C., Lipchina, I., Escobar, S. L., Hochedlinger, K., Huang, J., Graeber, T. G., Braas, D., & Teitell, M. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.002 · Cited by 287 · see citing works
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Wang, Y., Deng, P., Liu, Y., Wu, Y., Chen, Y., Guo, Y., Zhang, S., Zheng, X., Zhou, L., Liu, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19360-1 · Cited by 259 · see citing works
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TeSlaa, T. A., & Teitell, M. A. (2014) · The EMBO Journal · doi:10.15252/embj.201490446 · Cited by 212 · see citing works
Self-citationRelevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine
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Gascón, S., Masserdotti, G., Russo, G. L., & Götz, M. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.06.011 · Cited by 177 · see citing works
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Fathollahipour, S., Patil, P. S., & Leipzig, N. D. (2018) · Cells Tissues Organs · doi:10.1159/000493162 · Cited by 101 · see citing works
Metabolism in pluripotency: Both driver and passenger?
Dahan, P., Lu, V., Nguyen, R., Kennedy, S. A. L., & Teitell, M. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000832 · Cited by 74 · see citing works
Self-citationLlorente, I. L., Xie, Y., Mazzitelli, J. A., Hatanaka, E. A., Cinkornpumin, J. K., Miller, D. R., Lin, Y., Lowry, W. E., & Carmichael, S. T. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6747 · Cited by 64 · see citing works
Self-citationCoelho, P., Fão, L., Mota, S., & Rego, A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101667 · Cited by 39 · see citing works
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Begum, A. N., Guoynes, C. D., Cho, J., Hao, J., Lutfy, K., & Hong, Y. (2015) · Stem Cell Research · doi:10.1016/j.scr.2015.10.014 · Cited by 43 · see citing works
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Ortega, J. A., Sirois, C. L., Memi, F., Glidden, N., & Zecevic, N. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw194 · Cited by 37 · see citing works
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Rust, R., Weber, R., Generali, M., Kehl, D., Bodenmann, C., Uhr, D., Wanner, D., Zürcher, K. J., Saito, H., Hoerstrup, S. P., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03610-5 · Cited by 37 · see citing works
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McMurtrey, R. J. (2017) · Stem Cells and Development · doi:10.1089/scd.2017.0066 · Cited by 37 · see citing works
Silveira, R. G., Ferrúa, C. P., do Amaral, C. C., Garcia, T. F., de Souza, K. B., & Nedel, F. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.01.009 · Cited by 37 · see citing works
Zhang, Q., Wang, Y., Zhang, W., Chen, X., Wang, J., Chen, J., & Luo, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9761-1 · Cited by 36 · see citing works
Graphene oxide-stabilized perfluorocarbon emulsions for controlled oxygen delivery.
Jalani, G., Jeyachandran, D., Church, R. B., & Cerruti, M. (2017) · Nanoscale · doi:10.1039/c7nr00378a · Cited by 25 · see citing works
Photobiomodulation‐Induced Differentiation of Immortalized Adipose Stem Cells to Neuronal Cells
George, S., Hamblin, M. R., & Abrahamse, H. (2020) · Lasers in Surgery and Medicine · doi:10.1002/lsm.23265 · Cited by 33 · see citing works
Yasui, T., Uezono, N., Nakashima, H., Noguchi, H., Matsuda, T., Noda-Andoh, T., Okano, H., & Nakashima, K. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.001 · Cited by 27 · see citing works
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Kang, P. J., Zheng, J., Lee, G., Son, D., Kim, I. Y., Song, G., Park, G., & You, S. (2019) · Metabolic Engineering · doi:10.1016/j.ymben.2019.02.003 · Cited by 29 · see citing works
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Zhi, Y., Zhu, Y., Wang, J., Zhao, J., & Zhao, Y. (2023) · Research · doi:10.34133/research.0273 · Cited by 24 · see citing works
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Weber, R., Rentsch, N. H., Buil, B. A., Generali, M., Nih, L. R., Tackenberg, C., & Rust, R. (2025) · Advanced Science · doi:10.1002/advs.202504154 · Cited by 10 · see citing works
The Ties That Bind: Glial Transplantation in White Matter Ischemia and Vascular Dementia
Carmichael, S. T., & Llorente, I. L. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01322-8 · Cited by 10 · see citing works
Isolation and Characterization of Vessel-Associated Stem/Progenitor Cells from Skeletal Muscle
Tonlorenzi, R., Rossi, G., & Messina, G. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6771-1_8 · Cited by 9 · see citing works
Gibson, G. E., & Thakkar, A. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.06.007 · Cited by 8 · see citing works
Hypoxia Regulation of Stem Cell
Liu, Y., Tsai, A., Yuan, X., Li, Y., & Ma, T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802734-9.00018-4 · Cited by 8 · see citing works
Radhakrishnan, S., Martin, C. A., Dhayanithy, G., Reddy, M. S., Rela, M., Kalkura, S. N., & Sellathamby, S. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00728 · Cited by 8 · see citing works
Okada, R., Onodera, K., Ito, T., Doyu, M., Okano, H. J., & Okada, Y. (2020) · Neuroscience Research · doi:10.1016/j.neures.2020.01.015 · Cited by 8 · see citing works
Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions
Lee, H., & Hong, I. (2020) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x15666200512105347 · Cited by 7 · see citing works
Mennen, R. H., de Leeuw, V. C., & Piersma, A. H. (2020) · Differentiation · doi:10.1016/j.diff.2020.07.001 · Cited by 6 · see citing works
Yamazaki, K., Fukushima, K., Sugawara, M., Tabata, Y., Imaizumi, Y., Ishihara, Y., Ito, M., Tsukahara, K., Kohyama, J., & Okano, H. (2016) · SLAS DISCOVERY · doi:10.1177/1087057116661291 · Cited by 6 · see citing works
Lukmanto, D., Khánh, V. C., Shirota, S., Kato, T., Takasaki, M. M., & Ohneda, O. (2019) · Stem Cells and Development · doi:10.1089/scd.2019.0101 · Cited by 5 · see citing works
Epigenetic Regulation of Human Neural Stem Cell Differentiation
Honda, M., Nakashima, K., & Katada, S. (2018) · Results and problems in cell differentiation · doi:10.1007/978-3-319-93485-3_5 · Cited by 5 · see citing works
Extracellular cues accelerate neurogenesis of induced pluripotent stem cell derived neuronsPreprint
Sharlow, E. R., Llaneza, D. C., Mendelson, A. J., Mingledorff, G. A., Porterfield, V. M., Salvati, K. A., Beenhakker, M. P., Bloom, G. S., & Lazo, J. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.17.456634 · Cited by 4 · see citing works
Delayed transplantation of neural stem cells improves initial graft survival following strokePreprint
Weber, R., Rentsch, N. H., Buil, B. A., Nih, L. R., Tackenberg, C., & Rust, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.13.638119 · Cited by 4 · see citing works
McMurtrey, R. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812636-3.00002-x · Cited by 2 · see citing works
Oxygen and the Spark of Human Brain Evolution: a Complex Systems AccountPreprint
Luppi, A., Rosas, F. E., Noonan, M. P., Mediano, P. A. M., Kringelbach, M. L., Carhart-Harris, R. L., Stamatakis, E. A., Vernon, A. C., & Turkheimer, F. (2022) · Preprints.org · doi:10.20944/preprints202206.0002.v1 · Cited by 2 · see citing works
Rebuilding the brain: A narrative review of glial transplantation in neurological diseases
Bonfoey, A. M., Li, L., Sun, B., Harris, O. A., & Luo, J. (2025) · Regenerative medicine reports . · doi:10.4103/regenmed.regenmed-d-25-00032 · Cited by 1 · see citing works
Mennen, R. H., de Leeuw, V. C., & Piersma, A. H. (2021) · Toxicology in Vitro · doi:10.1016/j.tiv.2021.105247 · Cited by 1 · see citing works
Fang, L., Feng, Z., Mei, J., Zhou, J., & Lin, Z. (2022) · PubMed Central · doi:10.12122/j.issn.1673-4254.2022.06.18 · Cited by 1 · see citing works
Wang, L., Zhuo, Y., He, Z., Xia, Y., & Lu, M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/598441 · Cited by 1 · see citing works
Barreto, S., Al-Zubaidi, M. A., Dale, T. P., Worrall, A. J., Kapacee, Z., Kimber, S. J., Sulé-Suso, J., Forsyth, N. R., & Rutter, A. V. (2022) · Preprints.org · doi:10.20944/preprints202203.0143.v1 · Cited by 1 · see citing works
Begum, A. N., & Hong, Y. (2017) · PubMed
Pappalardo, Z., Downie, B., Adams, B. A., & Lim, J. I. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.19.576329
Rust, R., Weber, R., Generali, M., Kehl, D., Bodenmann, C., Uhr, D., Wanner, D., Zürcher, K. J., Saito, H., Hoerstrup, S. P., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21151340
Akbari, H., Kashani, I. R., Yazdi, F. R., Pasbakhsh, P., & Mojaverrostami, S. (2026) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2026.110706
- Authors
- Xie, Y., Zhang, J., Lin, Y., Gaeta, X., Meng, X., Wisidagama, D. R. R., Cinkornpumin, J., Koehler, C. M., Malone, C. S., Teitell, M. A., & Lowry, W. E.
- Affiliations
- University of California, Los Angeles (US)
- California State University, Northridge (US)
- California NanoSystems Institute (US)
- Corresponding author
- Teitell, Michael A.
- Lowry, William E.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 3
- Issue
- 5
- Pages
- 743-757
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4235163
- OpenAlex
- W2016736810
- Cited by
- 65
- References
- 49
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 2 · 2014: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- John Spoor Broome Library Institutional Repository (California State University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- CSUN ScholarWorks (California State University, Northridge) (submittedVersion)
- Funders
- American Heart Association
- Leukemia and Lymphoma Society
- China Scholarship Council
- National Cancer Institute (R01CA107300, R01CA185189, R01 CA90571, R01CA090571, R01CA156674)
- National Institute of General Medical Sciences (P01GM081621, R01GM073981, P01GM099134, F31GM113641, P01GM99134)
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- oxygen partial pressure, hypoxia, human embryonic stem cells, hypoxia-inducible factor, c-Myc, neuronal differentiation, glial differentiation, cell fate determination, small molecules
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Cell Differentiation, Cell Line, Cells, Cultured, Humans, Oxygen, Signal Transduction, Cell Hypoxia, Proto-Oncogene Proteins c-myc, RNA-Binding Proteins, Oligonucleotide Array Sequence Analysis, RNA Interference, MicroRNAs, Cell Proliferation, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Neurogenesis, Neural Stem Cells, Transcriptome
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