Evidence map›Paper›PMID 39501364›Full record

ArticleStem cell research & therapy2024

HES1 revitalizes the functionality of aged adipose-derived stem cells by inhibiting the transcription of STAT1.

Chengcheng Li, Sen Ren, Chengqi Yan, Cheng Wang, Tao Jiang, Yu Kang, Jing Chen, Hewei Xiong, Jiahe Guo, Guoyong Jiang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Chengcheng Li *Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Sen Ren *Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Chengqi YanDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Cheng WangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Tao JiangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Yu KangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Jing ChenDepartment of Dermatology, Wuhan No.1 Hospital, Wuhan, Hubei, 430000, China.
Hewei XiongDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Jiahe GuoDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Guoyong JiangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Shuoyuan LiuDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Pengjuan NieDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Zhenbing ChenDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. zbchen@hust.edu.cn.ORCID 0000-0003-2828-866X

Funding

National Natural Science Foundation of China 82172221National Natural Science Foundation of China 82302814
6 · The paper itself

Abstract

backgroundThe effectiveness of adipose-derived stem cells (ADSCs) in therapy diminishes with age. It has been reported that transcription factors (TFs) play a crucial role in the aging and functionality of stem cells. Nevertheless, there is limited understanding regarding the involvement of TFs in the aging mechanism of ADSCs.

methodsRNA sequencing (RNA-seq) was utilized to discern the differentially expressed genes in ADSCs obtained from donors of varying ages. TFs exhibiting significant variations across age groups were identified and subsequently validated. ADSCs were manipulated to exhibit either enhanced expression or reduced levels of HES1 and STAT1 via lentivirus transfection and small interfering RNA (siRNA) techniques. The impact of these genetic alterations on ADSCs' proliferation, migration, and cellular senescence was assessed using EdU, transwell, and senescence-activated β-galactosidase (SA-β-gal) staining assays. The DNA sequences bound by HES1 were investigated through the CUT & Tag assay. Lastly, the therapeutic efficacy of aged ADSCs with HES1 overexpression was evaluated in skin injury model of male Sprague-Dawley rats.

results678 genes showed differential expression between ADSCs obtained from young and old donors (Y-ADSCs and O-ADSCs), with 47 of these genes being TFs. Notably, the expression of the TF hairy and enhancer of split 1 (HES1) was notably reduced in ADSCs from old donors. Introducing HES1 overexpression in aged ADSCs resulted in improved cellular function and the suppression of cellular senescence, while reducing HES1 levels in young ADSCs had the opposite effect. Mechanistically, HES1 was found to interact with the promoter region of another TF, signal transducer and activator of transcription 1 (STAT1), to inhibit its transcription. Knocking down STAT1 could fully reverse the negative effects caused by decreased HES1 in ADSCs, leading to a reduction in the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Ultimately, restoring HES1 expression in aged ADSCs demonstrated enhanced therapeutic potential in promoting skin wound healing.

conclusionHES1 acts as an inhibitor of cellular senescence in the aging progression of ADSCs through the modulation of STAT1 expression, suggesting a promising avenue for rejuvenating senescent ADSCs and improving wound healing.

Indexed as

Adipose TissueCellular SenescenceRats, Sprague-DawleySTAT1 Transcription FactorTranscription Factor HES-1AnimalsCell ProliferationHumansMaleRatsStem CellsHES1 protein, humanHes1 protein, ratSTAT1 protein, humanStat1 protein, ratSTAT1 Transcription FactorTranscription Factor HES-1Adipose stem cellAgingHES1STAT1Transcription factors

Identifiers

PMID39501364
PMCPMC11539794

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.