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Cited by 45Single-cell and spatial transcriptomicsCongenital heart defects researchCardiac electrophysiology and arrhythmias

Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging

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Zhang, Yiyuan, Zheng, Yandong, Wang, Si, Fan, Yanling, Ye, Yanxia, Jing, Yaobin, Liu, Zunpeng, Yang, Shanshan +10 more·2022·Protein & Cell
DOI 10.1093/procel/pwac038PMC PMC10120965
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Abstract

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

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  • Fibrosis levels are elevated in heart and intestine of aged mice.

    “In addition, levels of fibrosis were elevated in both the heart and intestine of aged mice”

    From Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging (2024) · cites this paper as [36]

    The Results section on age-related changes in cynomolgus monkey left ventricles reports increased fibrotic areas in aged hearts. It does not establish elevated fibrosis in aged mice or in the intestine; the population and second organ in the claim are unsupported. No page number is available in our copy. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Zhang, Y., Zheng, Y., Wang, S., Fan, Y., Ye, Y., Jing, Y., Liu, Z., Yang, S., Xiong, M., Yang, K., Hu, J., Che, S., Chu, Q., Song, M., Liu, G.-H., Zhang, W., Ma, S., & Qu, J.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Capital Medical University (CN)
Corresponding author
  • Liu, Guang-Hui
  • Zhang, Weiqi
  • Ma, Shuai
  • Qu, Jing
ORCID
Venue
Protein & Cell
Publisher
Springer Science and Business Media LLC
Published
2022-09-06
Volume
14
Issue
4
Pages
279-293
ISSN
  • 1674-800X (ISSN-L)
  • 1674-8018
DOI
10.1093/procel/pwac038
PMC
PMC10120965
OpenAlex
W4294770424
Cited by
45
References
10
Citations by year
2026: 5 · 2025: 9 · 2024: 12 · 2023: 15 · 2022: 4
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Protein & Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2018YFC2000100)
  • Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000)
  • National Natural Science Foundation of China (81921006, 92149301, 92168201, 82125011, 91949209, 92049304, 92049116, 32121001, 82192863, 82122024, 82071588, 81901432, 32000510, 81861168034, 32000500, 81901433, 81870228, 81922027)
  • K. C. Wong Education Foundation (GJTD-2019-06, GJTD-2019-08)
  • Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes (11000022T000000461062)
  • CAS Project for Young Scientists in Basic Research (YSBR-012)
  • Youth Innovation Promotion Association of CAS (E1CAZW0401, 2022083)
  • Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301, CAS-WX2022SDC-XK14)
  • Tencent Foundation (2021-1045)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
cardiac aging, FOXP1, cardiomyocytes, single-nucleus transcriptomics, Macaca fascicularis, transcriptional regulatory networks, cardiomyocyte senescence, cardiomyocyte hypertrophy, heart failure, left ventricle, transcription factor downregulation
MeSH terms
Aged, Aging, Animals, Humans, Macaca fascicularis, Primates, Repressor Proteins, Myocytes, Cardiac, Forkhead Transcription Factors, Transcriptome

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