LMCD1 facilitates the induction of pluripotency via cell proliferation, metabolism, and epithelial‐mesenchymal transition

Somatic cell reprogramming was achieved by lentivirus mediated overexpression of four transcription factors called OSKM: OCT3/4, SOX2, KLF4, and c‐MYC but it was not very efficient. Here, we reported that the transcription factor, LMCD1 (LIM and cysteine rich domains 1) together with OSKM can induce...

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Vydáno v:Cell biology international Ročník 46; číslo 9; s. 1409 - 1422
Hlavní autoři: Ye, Zhikai, Chen, Ge, Hou, Cuicui, Jiang, Zhenlong, Wang, Erkang, Wang, Jin
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Wiley Subscription Services, Inc 01.09.2022
Témata:
AKT protein
Cell growth
Cell Proliferation
Cellular Reprogramming
Co-Repressor Proteins - genetics
Epigenetics
Epithelial-Mesenchymal Transition - genetics
epithelial‐mesenchymal transition
Fibroblasts
Fibroblasts - metabolism
Glycolysis
Humans
Induced Pluripotent Stem Cells - metabolism
Inhibitory postsynaptic potentials
Intracellular Signaling Peptides and Proteins - metabolism
KLF4 protein
LIM Domain Proteins - genetics
LMCD1
Mesenchyme
Myc protein
Oct-4 protein
Pluripotency
reprogramming efficiency
Stem cells
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
epithelial-mesenchymal transition
cell proliferation
reprogramming efficiency
LMCD1
epigenetics
glycolysis
ISSN:1065-6995, 1095-8355, 1095-8355
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Shrnutí:Somatic cell reprogramming was achieved by lentivirus mediated overexpression of four transcription factors called OSKM: OCT3/4, SOX2, KLF4, and c‐MYC but it was not very efficient. Here, we reported that the transcription factor, LMCD1 (LIM and cysteine rich domains 1) together with OSKM can induce reprogramming of human dermal fibroblasts into induced pluripotent stem cells (iPSCs) more efficiently than OSKM alone. At the same time, the number of iPSCs clones were reduced when we knocked down LMCD1. Further study showed that LMCD1 can enhance the cell proliferation, the glycolytic capability, the epithelial‐mesenchymal transition (EMT), and reduce the epigenetic barrier by upregulating epigenetic factors (EZH2, WDR5, BMI1, and KDM2B) in the early stage of reprogramming, making the cells more accessible to gain pluripotency. Additional research suggested that LMCD1 can not only inhibit the developmental gene GATA6, but also promote multiple signaling pathways, such as AKT and glycolysis, which are closely related to reprogramming efficiency. Therefore, we identified the novel function of the transcription factor LMCD1, which reduces the barriers of the reprogramming from somatic to pluripotent cells in several ways in the early stage of reprogramming.
Bibliografie:ObjectType-Article-1
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ISSN:1065-6995
1095-8355
1095-8355
DOI:10.1002/cbin.11858