Evidence map›Paper›PMID 36056448›Full record

ArticleCell & bioscience2022

Induced hepatic stem cells maintain self-renewal through the high expression of Myc coregulated by TET1 and CTCF.

Chen Wang, Xinlu Yu, Sai Ding, Yang Liu, Hongxia Zhang, Jingbo Fu, Bing Yu, Haiying Zhu

Open access · goldAbstract read
In one paragraph

Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 57% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Chen Wang *Department of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Xinlu Yu *Department of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Sai Ding *Department of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Yang LiuDepartment of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Hongxia ZhangDepartment of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Jingbo FuDepartment of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
Bing YuDepartment of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China. smmucellyu@163.com.ORCID http://orcid.org/0000-0002-3421-8601
Haiying ZhuDepartment of Cell Biology, Naval Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, People's Republic of China. hyzhu@smmu.edu.cn.
Second Military Medical University · CN

Funding

Foundation strengthening program in technical field of China 2019-JCJQ-JJ-068National Natural Science Foundation of China 31471284National Natural Science Foundation of China 31771511National Natural Science Foundation of China 32171387National Natural Science Foundation of China 82173369
6 · The paper itself

Abstract

backgroundInduced hepatic stem cells (iHepSCs) with the capacities of self-renewal and bidifferentiation into hepatocytes and cholangiocytes were generated from mouse embryonic fibroblasts (MEFs) by lineage reprogramming in our previous research. However, the mechanism of iHepSC self-renewal has not been elucidated. Active demethylation regulated by Tet1 plays an important role in the self-renewal of stem cells, including pluripotent stem cells and adult stem cells. Here, we investigated the role and mechanism of Tet1-regulated demethylation in the self-renewal of iHepSCs.

methodsThe methylation levels and the expression of Tet1 in iHepSCs and MEFs were analyzed by immunofluorescent staining, quantitative reverse transcription PCR and western blotting. Then, the effects of Tet1 knockdown on the proliferation and self-renewal of iHepSCs were analyzed by CCK8, colony formation, and sphere formation assays. The mechanism by which Tet1 regulates the self-renewal of iHepSCs was investigated by chromatin immunoprecipitation, bisulfite sequence PCR, and methylation-sensitive restriction endonuclease-PCR.

resultsThe high level of 5hmC and the low level of 5mC in iHepSCs were accompanied by high expression of Tet1. After Tet1 expression was knocked down by shRNA in iHepSCs, the proliferation and self-renewal capacities were inhibited, and the expression of Myc was also decreased. The higher expression level of Myc in iHepSCs maintained its self-renewal and was regulated by Tet1, which directly binds to CBS-1 and site A regions of the Myc promoter and demethylates the CpG cytosine. In addition, CTCF also binds to the CBS-1 and site A regions of the Myc promoter and regulates Myc expression along with TET1.

conclusionThe self-renewal of iHepSCs was maintained by the higher expression of Myc, which was coregulated by TET1 and CTCF. This study may provide new insights into the self-renewal of stem cells, which can promote the research and application of 'reprogrammed' stem cells.

Indexed as

CtcfInduced hepatic stem cellMycSelf-renewalTet1

Identifiers

PMID36056448
PMCPMC9440563
OpenAlexW4294276809

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