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Project description:Potential MDDC reprogramming when exposed to BKPyV
| PRJNA647826 | ENA
Project description:Somatic cell reprogramming in vitro prior to nuclear transfer is one strategy expected to improve clone survival during development. In this study, we investigated the reprogramming extent of fish fin somatic cells after in vitro exposure to Xenopus egg extract and subsequent culture. Using a cDNA microarray approach, we observed drastic changes in the gene expression profile of the treated cells. Several actors of the TGFbeta and Wnt/beta-catenin signaling pathways, as well as some mesenchymal markers, were inhibited in treated cells, while several epithelial markers were upregulated. This was associated with morphological changes of the cells in culture, suggesting that egg extract drove somatic cells towards a mesenchymal-epithelial transition (MET), the hallmark of somatic reprogramming in iPSCs. However, treated cells were also characterized by a strong decrease in de novo lipid biosynthesis metabolism, the lack of re-expression of pou2 and nanog pluripotency markers, and absence of DNA methylation remodeling of their promoter region. In all, this study showed that Xenopus egg extract treatment initiated an in vitro reprogramming of fin somatic cells in culture. Although not thorough, the induced changes have primed the somatic chromatin for a better embryonic reprogramming upon nuclear transfer.
2023-01-01 | GSE205854 | GEO
Project description:ES cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in iPS cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation, and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency-genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process. ChIP-Seq for H3K4me3 and H3K4me2 in murine shLuc and shKdm5b 4TF-MEFs (tetO-Pou5f1,-Sox2,-Klf4,-c-Myc) at 48h.
2013-10-14 | E-GEOD-47123 | biostudies-arrayexpress
Project description:ES cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in iPS cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation, and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency-genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process. RNA-Seq of undifferentiated and embryoid body (EB) differentiated murine shLuc and shKdm5b ES cells
2013-10-14 | E-GEOD-47124 | biostudies-arrayexpress
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192752 | GEO
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192738 | GEO
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192727 | GEO
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192787 | GEO
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192770 | GEO
Project description:Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
2022-09-15 | GSE192735 | GEO