Dataset Information

Dux promotes OGS-Epigenetic-MET network during early iPSC reprogramming via H3K18la recruiting Brg1

ABSTRACT: The process of iPSC reprogramming involves various critical events such as somatic gene shutdown, mesenchymal-epithelial transition (MET), metabolism reprogramming, and epigenetic rewiring. These events interweave and influence each other leading to the formation of the iPSC reprogramming network, thus there appears to be a key element regulating this network. Dux has essential research value by promoting totipotency in the process of transition from ESC to 2C-like ESC and has not been discussed in depth in iPSC reprogramming process. This paper focused on the H3K18la modification linking the OGS-Epigenetic-MET network, which improved the efficiency for iPSC reprogramming via Dux overexpression. Dux promoted H3K18la via metabolism switch, and recruiting P300 through its C-terminal domain, resulting in increasing reprogramming. By using H3K18la regulators, we found the role H3K18la played in promoting MET. We performed proteomic detection of H3K18la by IP combined with MS and found that H3K18la specifically recruited Brg1 in iPSCs. During reprogramming, H3K18la and Brg1 enriched on promoters of epithelial-related genes and pluripotency-related genes. Overall, our work highlights H3K18la as a powerful trigger in the early reprogramming and reveals Dux as a regulator for increasing H3K18la. Brg1 was first demonstrated binding to H3K18la and identified as a reader of lactylation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell, Cell Culture

SUBMITTER: Xinglin Hu

LAB HEAD: Xinglin Hu

PROVIDER: PXD043547 | Pride | 2026-02-23

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	DE475DA_MEF_1_Slot1-30_1_22732.d.zip	Other
	DE475DA_MEF_2_Slot1-31_1_22733.d.zip	Other
	DE475DA_MEF_3_Slot1-32_1_22734.d.zip	Other
	DE475DA_iPSC_1_Slot1-33_1_22736.d.zip	Other
	DE475DA_iPSC_2_Slot1-34_1_22737.d.zip	Other

Items per page:

1 - 5 of 8

Publications

Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader.

Hu Xinglin X Huang Xingwei X Yang Yue Y Sun Yuchen Y Zhao Yanhua Y Zhang Zhijing Z Qiu Dan D Wu Yanshuang Y Wu Guangming G Lei Lei L

Nucleic acids research 20240601 10

The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor known to promote totipotency during the transition from embryonic stem cells (ESC) to 2C-like ESC ( ...[more]

PMID: 38512058

Similar Datasets

Project description:Since the first generation of induced Pluripotent Stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights Mesenchymal-Epithelial Transition (MET) as a roadblock, but also faces more severe difficulties to attain a pluripotent state even post-MET. Also, in contrast to previous findings, more efficient cassettes can reprogram both wild type and Nanog-/- fibroblasts with comparable efficiencies, routes and kinetics, rebutting previous studies that Nanog is critical for iPSC generation. We revealed that the 9 amino acids in the N-terminus of Klf4 in polycistronic reprogramming cassettes are the dominant factor causing these critical differences. Our data establishes that some reprogramming roadblocks are system-dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. The aim of the experiment is to compare the reprogramming pathways driven by two different polycistronic cassettes (MKOS and OKMS). We have isolated cells at intermediate stages of both MKOS and OKMS reprogramming and analysed their gene expression profiles. 2N- are CD44- ICAM1-, Nanog-GFP-, 3N- are CD44- ICAM1+, Nanog-GFP-, 3N+ are CD44- ICAM1+, Nanog-GFP+, all from day 10 of reprogramming. MKOS/OKMS iPSCs are established iPSC clones, TNG an Embryonic Stem Cell line carrying a Nanog-GFP reporter published in Chambers et al. Cell, 113, 643-655, from this line TNG MKOS and OKMS Embryonic Stem Cells were generated after targeting the Sp3 locus with the MKOS or the OKMS cassette respectively,E14 a reference Embryonic Stem Cell line and MEF are Mouse Embryonic Fibroblasts either wild type or generaterd from TNG MKOS or OKMS ESCs. D6 is the D6s4B5 iPSC line published in O'Malley et al. Nature, 499, 88-91.