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Kramer's review highlights emerging evidence that suggests that iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies [ 75].
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It has been suggested that many of the differences between murine pluripotent stem cells (mPSCs) and hPSCs could be attributed to mPSC and hPSC cultures representing different states of pluripotency and that hPSCs can move between these states with changes in culture conditions [ 22, 23].
In conclusion, our data suggest that expression profiling can serve as an informative benchmark to distinguish different states of primed and naive human pluripotency.
It has become clear that no single transcriptional state can be associated with, for example the state of pluripotency, even though individual cells may be functionally pluripotent 54.
Based on the gene expression and culture requirements, recent studies suggest that human ESCs are in a pluripotent state similar to mouse epiblast-derived stem cells (EpiSCs), and different from mouse ESCs derived from earlier blastocyst stage, which were proposed to be in a naïve ground state of pluripotency [25].
These inhibitors generate human pluripotent cells in which transcription factors associated with the ground state of pluripotency are highly upregulated and bivalent chromatin domains are depleted.
Finally, we tested whether NANOG upregulation by iVPR may facilitate hESCs to enter the naïve state of pluripotency.
Open image in new window Figure 5 Upregulation of NANOG by dCas9-VPR promoted clonogenicity and the naïve state of pluripotency.
Hence, the G1 phase cells appeared to be more susceptible to differentiation, particularly when ESCs self-renewed in the naïve state of pluripotency.
The cloning of Dolly the Sheep over a decade ago demonstrated that adult somatic cells could reprogrammed back to a state of pluripotency [1].
Karyotyping was performed on iPS lines 1 and 2. ESCs are maintained in a state of pluripotency by a precise regulation of numerous intrinsic and extrinsic factors.
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