The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human
Open accessAbstract
Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground-state transcription factors, TFCP2L1 or KLF4, has marginal impact on conventional human pluripotent stem cells but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground-state pluripotency in human cells.
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Self-citationA ROCK inhibitor permits survival of dissociated human embryonic stem cells
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“…reset cells could be channeled into adherent differentiation by exposure to FGF/KSR and application of protocols developed for conventional PSC. Cells exchanged into FGF/ KSR for a few days responded to activin andWnt3A (Kroon et al., 2008) by differentiation into definitive endoderm (Figure 2F).”
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“In these conditions, reset cells could form undifferentiated colonies on Matrigel or laminin 511-E8 (Nakagawa et al., 2014) (Figure 1K).”
BackgroundDefining an essential transcription factor program for naïve pluripotency
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A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development
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The impact of cellular metabolism on chromatin dynamics and epigenetics
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Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535
“TCA cycle activity also varies with PSC identity in human ESCs, which display glutamine independence and increased mitochondrial respiration upon conversion to a more naïve state (215, 216).”
Background
Metadata
- Authors
- Takashima, Y., Guo, G., Loos, R., Nichols, J., Ficz, G., Krueger, F., Oxley, D., Santos, F., Clarke, J., Mansfield, W., Reik, W., Bertone, P., & Smith, A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 158
- Issue
- 6
- Pages
- 1254-1269
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2045067641
- Cited by
- 952
- References
- 10
- FWCI
- 34.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Takashima, Y., Guo, G., Loos, R., Nichols, J., Ficz, G., Krueger, F., Oxley, D., Santos, F., Clarke, J., Mansfield, W., Reik, W., Bertone, P., & Smith, A. (2014). Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human. Cell. https://doi.org/10.1016/j.cell.2014.08.029
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
