Project description:SeVdp(KOSM) vector can efficiently induce a somatic cell reprogramming in many types of cells. In contrast to SeVdp(KOSM), SeVdp(GKOSM) only induce partially-reprogrammed cells.
Project description:Uncovering novel factors in induced pluripotent stem cells is of great significance for understanding the molecular mechanisms of cell fate determination and advancing somatic cell reprogramming technology. The applicant has, for the first time, discovered that overexpressing RORA significantly enhances somatic cell reprogramming, suggesting that RORA may be one of the key factors in this process. This project aims to investigate the molecular mechanisms by which RORA promotes reprogramming and, based on these findings, establish a more efficient somatic cell reprogramming system. This research is expected to reveal new reprogramming factors and develop a more efficient somatic cell reprogramming system, thereby providing new insights and perspectives for understanding the molecular mechanisms of somatic cell reprogramming and cell fate transition.
Project description:This is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state.
Project description:Somatic cells acclimate to changes in the environment by temporary reprogramming. Much has been learned about transcription factors that induce these cell-state switches in both plants and animals, but how cells rapidly modulate their proteome remains elusive. Here, we show rapid induction of autophagy during temporary reprogramming in plants triggered by phytohormones, immune and danger signals. Quantitative proteomics following sequential reprogramming revealed that autophagy is required for timely decay of previous cellular states and for tweaking the proteome to acclimate to the new conditions. Signatures of previous cellular programs thus persist in autophagy deficient cells, affecting cellular decision-making. Concordantly, autophagy deficient cells fail to acclimatize to dynamic climate changes. Similarly, they have defects in dedifferentiating into pluripotent stem cells, and redifferentiation during organogenesis. These observations indicate that autophagy mediates cell state switches that underlie somatic cell reprogramming in plants and possibly other organisms, and thereby promotes phenotypic plasticity.
Project description:This is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state.
Project description:This is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state.
Project description:Tet1 is a hydroxylase known for its role in the conversion of 5-methylcytosines (5mC) to 5-hydroxymethylcytosines (5hmC) involved in the possible active demethylation process and gene expression regulation1-5.M-BM- As somatic cell reprogramming involves the re-activation of pluripotency genes and the silencing of somatic ones6, it remains unclear whether Tet1 plays a positive or negative role in the reprogramming process. Here we show that Tet1 deficiency enhances reprogramming and its overexpression impairs reprogramming. Mechanistically, we demonstrated that Tet1 represses the early obligatory process of mesenchymal to epithelial transition (MET) during reprogramming7,8. Thus, our findings not only define a negative role for Tet1 in somatic cell reprogramming, but also suggest that the Tet enzymes regulate cell fate through distinctive mechanisms. Examination of genome DNA hmC modifications in 2 conditions: individually overexpressed Tet1CD or Tet2CD during MEF reprogramming; Examination of mRNA levels in five different conditions: individually overexpressed DR or Tet1CD or Tet1CDmut or Tet2CD or Tet2CDmut, during MEF reprogrammig.
Project description:We have developed a nuclear transfer (NT) system in which somatic nuclei are transplanted into mouse embryos arrested at the 4-cell stage. The transplanted somatic nuclei show swelling and epigenetic reprogramming towards 4-cell-like nuclei. To assess genome-wide transcriptional reprogramming of the injected nuclei, the newly transcribed genes in NT embryos were examined by RNA-seq analyses. As a control, NT was also performed using mouse embryos at the 2-cell stage.
Project description:This is the first study deciphering the global regulatory network that drives human somatic cells during epigenetic rewiring towards the pluripotent state.