Evidence map›Paper›PMID 33038325›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

ESC-sEVs Rejuvenate Aging Hippocampal NSCs by Transferring SMADs to Regulate the MYT1-Egln3-Sirt1 Axis.

Guowen Hu, Yuguo Xia, Bi Chen, Juntao Zhang, Liangzhi Gong, Yu Chen, Qing Li, Yang Wang, Zhifeng Deng

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

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

25 citing papers in PubMed, 46 citations in OpenAlex.

  1. 3D-bioprinted adipose-derived stem cell-secreted GAS6Journal of nanobiotechnology · 2026
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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

9 authors at 2 institutions in 1 country.

Guowen HuDepartment of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Yuguo XiaDepartment of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Bi ChenInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Juntao ZhangInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Liangzhi GongInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Yu ChenInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Qing LiInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: liqing_236@aliyun.com.
Yang WangInstitute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: wangyang63@sjtu.edu.cn.
Zhifeng DengDepartment of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zfdeng@sjtu.edu.cn.
Shanghai Jiao Tong University · CNNanchang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cell (NSC) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSC (H-NSC) senescence, as well as the function and mechanism of embryonic stem cell-derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSC senescence. We found a progressive cognitive impairment, as well as age-related H-NSC senescence, in mice. ESC-sEV treatment significantly alleviated H-NSC senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD family members 4 (SMAD4) and 5 (SMAD5) to activate MYT1, which downregulated egl-9 family hypoxia inducible factor 3 (Egln3), followed by activation of hypoxia inducible factor 2 subunit α (HIF-2α), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (Sirt1) successively. Taken together, our results indicated that H-NSC senescence caused cellular exhaustion, neurogenesis reduction, and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.

Indexed as

AnimalsCell DifferentiationCellular SenescenceDNA-Binding ProteinsEmbryonic Stem CellsExtracellular VesiclesGene Expression ProfilingGene Expression RegulationHippocampusHypoxia-Inducible Factor-Proline DioxygenasesMiceMice, KnockoutNeural Stem CellsSignal TransductionSirtuin 1Transcription FactorsDNA-Binding ProteinsHypoxia-Inducible Factor-Proline DioxygenasesMyt1 protein, mouseSirt1 protein, mouseSirtuin 1Transcription FactorsagingESC-sEVshippocampal NSCsMYT1senescence

Identifiers

PMID33038325
PMCPMC7791087
OpenAlexW3090865474

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.