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Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation
Open accessAbstract
Summary Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. Here, we show that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment of and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. However, remaining differences between naïve hESCs and embryonic cells related to monoallelic XIST expression and non-random X-inactivation highlight the need for further culture improvement. As the naïve state reset Xi abnormalities seen in primed hESCs it may provide cells better suited for downstream applications.
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Cited by
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Epigenetic resetting of human pluripotency
Guo, G., von Meyenn, F., Rostovskaya, M., Clarke, J., Dietmann, S., Baker, D., Sahakyan, A., Myers, S., Bertone, P., Reik, W., et al. (2017) · Development · doi:10.1242/dev.146811 · Cited by 319
Self-citationPrinciples of signaling pathway modulation for enhancing human naive pluripotency induction
Bayerl, J., Ayyash, M., Shani, T., Manor, Y. S., Gafni, O., Massarwa, R., Kalma, Y., Aguilera-Castrejon, A., Zerbib, M., Amir, H., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.04.001 · Cited by 165
Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence
Ohashi, M., Korsakova, E., Allen, D., Lee, P., Fu, K., Vargas, B. S., Cinkornpumin, J., Salas, C., Park, J. C., Germanguz, I., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.04.001 · Cited by 80
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Metadata
- Authors
- Sahakyan, A., Kim, R., Chronis, C., Sabri, S., Bonora, G., Theunissen, T. W., Kuoy, E., Langerman, J., Clark, A. T., Jaenisch, R., & Plath, K.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 20
- Issue
- 1
- Pages
- 87-101
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2561883112
- Cited by
- 254
- References
- 0
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sahakyan, A., Kim, R., Chronis, C., Sabri, S., Bonora, G., Theunissen, T. W., Kuoy, E., Langerman, J., Clark, A. T., Jaenisch, R., & Plath, K. (2017). Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation. Cell Stem Cell. https://doi.org/10.1016/j.stem.2016.10.006
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