Knocking down of UTX in NCCIT cells enhance cell attachment and promote early neuronal cell differentiation

Mandal, Chanchal; Jung, Kyoung Hwa; Kang, Sung Chul; Choi, Mi Ran; Park, Kyoung Sun; Chung, Il Yup; Chai, Young Gyu

doi:10.1007/s13206-015-9302-4

Cited by 2 publications

(3 citation statements)

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“…The NCCIT cell line is derived from embryonal carcinoma and thus exhibits a gene expression signature highly similar to human embryonic stem cells ( Fuentes et al, 2018 ; Barnada et al, 2022 ). Importantly, NCCITs treated for 7 days with RA differentiate into intermediate neural progenitor-like cells expressing both PAX6 and TBR2 ( Mandal et al, 2015 ; Fig. 7 A).…”

Section: Resultsmentioning

confidence: 99%

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

et al. 2022

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The hippocampus is associated with essential brain functions such as learning and memory. Human hippocampal volume is significantly greater than expected when compared to non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in the evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced Pluripotent Stem Cells into TBR2-positive hippocampal intermediate progenitors (hpIPCs). We find that the gene networks active in hpIPCs are significantly different between humans and chimpanzees, with ∼2,500 genes differentially expressed. We demonstrate that species-specific transposon-derived enhancers contribute to these transcriptomic differences. Young transposons, predominantly Endogenous Retroviruses (ERVs) and SINE-Vntr-Alus (SVAs), were co-opted as enhancers in a species-specific manner. Human-specific SVAs provided substrates for thousands of novel TBR2 binding sites, and CRISPR-mediated repression of these SVAs attenuates the expression of ∼25% of the genes that are upregulated in human intermediate progenitors relative to the same cell population in the chimpanzee.

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Section: Resultsmentioning

confidence: 99%

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

et al. 2022

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show abstract

“…The NCCIT cell line is derived from embryonal carcinoma and thus exhibits a gene expression signature highly similar to human embryonic stem cells (Fuentes et al, 2018). Importantly, NCCITs treated for 7 days with RA differentiate into intermediate neural progenitor-like cells expressing both PAX6 and TBR2 (Mandal et al, 2015; Fig 7A). We cloned a stable NCCIT line with a permanently incorporated doxycycline-inducible, catalytically-dead Cas9 fused to a repressive KRAB domain (dCas9-KRAB).…”

Section: Resultsmentioning

confidence: 99%

“…The NCCIT cell line is derived from embryonal carcinoma and thus exhibits a gene expression signature highly similar to human embryonic stem cells (Fuentes et al, 2018; Barnada et al, 2022). Importantly, NCCITs treated for 7 days with RA differentiate into intermediate neural progenitor-like cells expressing both PAX6 and TBR2 (Mandal et al, 2015; Fig 7A). RNA-seq tpms suggest very strong correlation between RA-treated NCCITs and human day-5 hpIPCs (Pearson correlation p < 2.2 × 10 ×16 , R=0.99).…”

Section: Resultsmentioning

confidence: 99%

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

Patoori

Barnada²,

Trizzino³

2021

Preprint

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The hippocampus is associated with essential brain functions such as learning and memory. Human hippocampal volume is significantly greater than expected when compared to non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in the evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced Pluripotent Stem Cells into TBR2-positive hippocampal intermediate progenitors (hpIPCs). We find that the gene networks active in hpIPCs are significantly different between humans and chimpanzees, with ~2,500 genes differentially expressed. We demonstrate that species-specific transposon-derived enhancers contribute to these transcriptomic differences. Young transposons, predominantly Endogenous Retroviruses (ERVs) and SINE-Vntr-Alus (SVAs), were co-opted as enhancers in a species-specific manner. Human-specific SVAs provided substrates for thousands of novel TBR2 binding sites, and CRISPR-mediated repression of these SVAs attenuates the expression of ~25% of the genes that are upregulated in human intermediate progenitors relative to the same cell population in the chimpanzee.Summary statementEvolution of human and chimpanzee hippocampal development was mediated by co-option of young retrotransposons into species-specific enhancers.

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Knocking down of UTX in NCCIT cells enhance cell attachment and promote early neuronal cell differentiation

Cited by 2 publications

References 26 publications

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

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