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Accession PRJCA024305
Title Role of Setdb1 in cell fate transitions between 2C-like state and pluripotent state
Relevance Medical
Data types Raw sequence reads
Organisms Mus musculus
Description Setdb1 is known as a histone H3K9 methyltransferase, which is essential for embryo development. Although several studies have shown that Setdb1 is required for the maintenance of pluripotency in mouse embryonic stem cells (ESCs) cultured in serum/LIF (SL) conditions, its function in cell fate decisions is largely unknown. Here, we report that under the "ground state" of pluripotency induced by two inhibitors (2i) of the MEK and GSK3 pathways, Setdb1 knockout does not induce trophectoderm (TE) differentiation as in SL conditions. In both conditions, Setdb1 deficiency reactivates 2C-like state genes, such as Zscan4 and Dux, which are repressed by Setdb1-dependent H3K9me3. Interestingly, Setdb1 deficiency only induces 2C-like totipotency in SL conditions. In the ground state, Setdb1-null ESCs maintain the expression of pluripotent markers, such as Nanog, resulting in a distinct stage with 2C-like totipotency. Furthermore, we found that in the ground state, Setdb1 deficiency induces rapid cell death by upregulating Ripk3 and subsequently activating RIPK1/RIPK3-dependent necroptosis.
Sample scope Monoisolate
Release date 2024-03-20
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2019YFA0110200
Submitter Jiekai    Chen  (chen_jiekai@gibh.ac.cn)
Organization Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Submission date 2024-03-14

Project Data

Resource name Description
BioSample (26)  show -
GSA (1) -
CRA015373 Role of Setdb1 in cell fate transitions between 2C-like state and pluripotent state