“…(2019) 8 ( Figure 3 C). We further compared our differentially expressed gene lists to the recently published 8-cell-like datasets, 36 , 37 , 38 and confirmed LEUTX expression in 8-cell-like cell population but not in primed stem cells.…”
Section: Resultssupporting
confidence: 54%
“…Recently developed methods to detect and enrich human 8-cell like cell populations among hESC or naive hPSC cultures provide a new tool for further characterization of human EGA-associated factors. 36 , 37 , 38 The 8 cell-like cells, however, represent minor subpopulation among hPSC or naive hPSC cultures and are unstable with a tendency to convert back to later developmental stages and as such are not feasible for the production of large amounts of cells expressing transgenic gene of interest. Figure 2 Genomics Overview (A) Overview of sequencing experiments and data analysis pipeline.…”
Section: Resultsmentioning
confidence: 99%
“…(2022). 38 The intensity of the color reflects the logFC of the gene in LEUTX STRT-Seq. (B) Validation of target genes up-regulated by LEUTX according to our STRT-Seq data.…”
Section: Resultsmentioning
confidence: 99%
“…Three recent studies identify a number of 8CLC signature and marker genes. 36 , 37 , 38 We compared the differentially expressed genes from our STRT-Seq to the identified 8CLC signature genes from these papers. Combined, all 1048 differentially expressed genes from LEUTX STRT-Seq match 377 genes identified in at least one of these papers ( Table S10 ).…”
Section: Resultsmentioning
confidence: 99%
“…Data from recent 8CLC papers 36 , 37 , 38 was used in the following way: when discussing ‘hub genes’ we refer to Mazid et al. 2022 36 Table S5 : Full list of 2,162 hub genes and their relative expression level in three cell states.…”
“…(2019) 8 ( Figure 3 C). We further compared our differentially expressed gene lists to the recently published 8-cell-like datasets, 36 , 37 , 38 and confirmed LEUTX expression in 8-cell-like cell population but not in primed stem cells.…”
Section: Resultssupporting
confidence: 54%
“…Recently developed methods to detect and enrich human 8-cell like cell populations among hESC or naive hPSC cultures provide a new tool for further characterization of human EGA-associated factors. 36 , 37 , 38 The 8 cell-like cells, however, represent minor subpopulation among hPSC or naive hPSC cultures and are unstable with a tendency to convert back to later developmental stages and as such are not feasible for the production of large amounts of cells expressing transgenic gene of interest. Figure 2 Genomics Overview (A) Overview of sequencing experiments and data analysis pipeline.…”
Section: Resultsmentioning
confidence: 99%
“…(2022). 38 The intensity of the color reflects the logFC of the gene in LEUTX STRT-Seq. (B) Validation of target genes up-regulated by LEUTX according to our STRT-Seq data.…”
Section: Resultsmentioning
confidence: 99%
“…Three recent studies identify a number of 8CLC signature and marker genes. 36 , 37 , 38 We compared the differentially expressed genes from our STRT-Seq to the identified 8CLC signature genes from these papers. Combined, all 1048 differentially expressed genes from LEUTX STRT-Seq match 377 genes identified in at least one of these papers ( Table S10 ).…”
Section: Resultsmentioning
confidence: 99%
“…Data from recent 8CLC papers 36 , 37 , 38 was used in the following way: when discussing ‘hub genes’ we refer to Mazid et al. 2022 36 Table S5 : Full list of 2,162 hub genes and their relative expression level in three cell states.…”
Mouse embryonic stem cells (mESCs) sporadically transition to a transient totipotent state that resembles blastomeres of the two‐cell (2C) embryo stage, which has been proposed to contribute to exceptional genomic stability, one of the key features of mESCs. However, the biological significance of the rare population of 2C‐like cells (2CLCs) in ESC cultures remains to be tested. Here we generated an inducible reporter cell system for specific elimination of 2CLCs from the ESC cultures to disrupt the equilibrium between ESCs and 2CLCs. We show that removing 2CLCs from the ESC cultures leads to dramatic accumulation of DNA damage, genomic mutations, and rearrangements, indicating impaired genomic instability. Furthermore, 2CLCs removal results in increased apoptosis and reduced proliferation of mESCs in both serum/LIF and 2i/LIF culture conditions. Unexpectedly, p53 deficiency results in defective response to DNA damage, leading to early accumulation of DNA damage, micronuclei, indicative of genomic instability, cell apoptosis, and reduced self‐renewal capacity of ESCs when devoid of 2CLCs in cultures. Together, our data reveal that transition to the privileged 2C‐like state is a major component of the intrinsic mechanisms that maintain the exceptional genomic stability of mESCs for long‐term self‐renewal.
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