Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA592060 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:N6-methyladenosine (m6A), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex. Ythdf2/3 deficiency further represses mesenchymal-to-epithelial transition (MET) and chromatin silencing at loci containing the TEAD motif, contributing to decreased reprogramming efficiency. Moreover, RNA interference of Tgfb1 or the Hippo signaling effectors Yap1, Taz, and Tead2 rescues Ythdf2/3-defective reprogramming. Overall, YTHDF2/3 couple RNA deadenylation and regulation with the clearance of somatic genes provides insights into iPSC reprogramming at the posttranscriptional level.
2020-08-19 | GSE156437 | GEO
Project description:Kdm2b regulates somatic reprogramming through variant PRC1 complex dependent function [RNA-seq]
| PRJNA369097 | ENA
Project description:Epidermal growth factor receptor (EGFR) signaling is constitutively activated in majority of GBM and is associated with a worse prognosis. Here we show that EGFR is responsible for overexpression of the m6A "reader" YTHDF2 in GBM through the EGFR/Src/ERK signaling pathway. YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR signaling stabilizes YTHDF2 protein through phosphorylation of YTHDF2 serine 39 and threonine 381 by ERK1/2. YTHDF2 is required for GBM cell proliferation, invasion and tumorigenesis. YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and HIVEP2, both are genes impacting glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells largely through downregulation of LXRA and HIVEP2. Further, YTHDF2 inhibits LXRA-dependent cholesterol homeostasis in GBM cells. Together, our findings extend the landscape of EGFR downstream circuit, uncover novel function for YTHDF2 in GBM tumorigenesis, and highlight an essential role of RNA m6A methylation in cholesterol homeostasis.
2020-10-08 | GSE142827 | GEO
Project description:Epidermal growth factor receptor (EGFR) signaling is constitutively activated in majority of GBM and is associated with a worse prognosis. Here we show that EGFR is responsible for overexpression of the m6A "reader" YTHDF2 in GBM through the EGFR/Src/ERK signaling pathway. YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR signaling stabilizes YTHDF2 protein through phosphorylation of YTHDF2 serine 39 and threonine 381 by ERK1/2. YTHDF2 is required for GBM cell proliferation, invasion and tumorigenesis. YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and HIVEP2, both are genes impacting glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells largely through downregulation of LXRA and HIVEP2. Further, YTHDF2 inhibits LXRA-dependent cholesterol homeostasis in GBM cells. Together, our findings extend the landscape of EGFR downstream circuit, uncover novel function for YTHDF2 in GBM tumorigenesis, and highlight an essential role of RNA m6A methylation in cholesterol homeostasis.
2020-10-08 | GSE142825 | GEO
Project description:Reprogramming to pluripotency through a somatic stem cell intermediate
| PRJNA189293 | ENA
Project description:ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming
| PRJNA262446 | ENA
Project description:In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.
| EGAD00001000384 | EGA
Project description:In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.
| EGAS00001000492 | EGA
Project description:In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unclear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.
| EGAD00001000798 | EGA
Project description:In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unclear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.
| EGAS00001000231 | EGA