Evidence map›Paper›PMID 37307473›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Leveraging single-cell RNA sequencing to unravel the impact of aging on stroke recovery mechanisms in mice.

Chenghao Jin, Yejie Shi, Ligen Shi, Rehana K Leak, Wenting Zhang, Kong Chen, Qing Ye, Sulaiman Hassan, Junxuan Lyu, Xiaoming Hu and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Monocyte-derived macrophages and their roles in ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  12. Article
  13. Review
  14. Insights gained from single-cell sequencing analysis of ischemic stroke.Frontiers in cell and developmental biology · 2026
    Review
  15. Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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 at 3 institutions in 1 country.

Chenghao JinPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Yejie ShiPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.ORCID 0000-0001-7502-9201
Ligen ShiPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Rehana K LeakGraduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA 15282.ORCID 0000-0003-2817-7417
Wenting ZhangPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.ORCID 0000-0002-2277-4686
Kong ChenDepartment of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Qing YePittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Sulaiman HassanPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Junxuan LyuPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Xiaoming HuPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.ORCID 0000-0002-5857-6243
R Anne StetlerPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
Michael V L BennettDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Jun ChenPittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213.
University of Pittsburgh · USAlbert Einstein College of Medicine · USDuquesne University · US

Funding

Activation of the RXR/PPARγ axis improves long-term outcomes after ischemic stroke in aged miceI01BX005290 · VA · VETERANS HEALTH ADMINISTRATION · PI CHEN, JUN · 2022 to 2025
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BLRD Research Career Scientist Award ApplicationIK6BX006298 · VA · VETERANS HEALTH ADMINISTRATION · PI CHEN, JUN · 2023 to 2025
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BLRD VA I01 BX003377BLRD VA I01 BX005290BLRD VA IK6 BX006298
6 · The paper itself

Abstract

Aging compromises the repair and regrowth of brain vasculature and white matter during stroke recovery, but the underlying mechanisms remain elusive. To understand how aging jeopardizes brain tissue repair after stroke, we performed single-cell transcriptomic profiling of young adult and aged mouse brains at acute (3 d) and chronic (14 d) stages after ischemic injury, focusing a priori on the expression of angiogenesis- and oligodendrogenesis-related genes. We identified unique subsets of endothelial cells (ECs) and oligodendrocyte (OL) progenitors in proangiogenesis and pro-oligodendrogenesis phenotypic states 3 d after stroke in young mice. However, this early prorepair transcriptomic reprogramming was negligible in aged stroke mice, consistent with the impairment of angiogenesis and oligodendrogenesis observed during the chronic injury stages after ischemia. In the stroke brain, microglia and macrophages (MG/MΦ) may drive angiogenesis and oligodendrogenesis through a paracrine mechanism. However, this reparative cell-cell cross talk between MG/MΦ and ECs or OLs is impeded in aged brains. In support of these findings, permanent depletion of MG/MΦ via antagonism of the colony-stimulating factor 1 receptor resulted in remarkably poor neurological recovery and loss of poststroke angiogenesis and oligodendrogenesis. Finally, transplantation of MG/MΦ from young, but not aged, mouse brains into the cerebral cortices of aged stroke mice partially restored angiogenesis and oligodendrogenesis and rejuvenated sensorimotor function and spatial learning and memory. Together, these data reveal fundamental mechanisms underlying the age-related decay in brain repair and highlight MG/MΦ as effective targets for promoting stroke recovery.

Indexed as

Endothelial CellsStrokeAnimalsBrainMacrophagesMiceSequence Analysis, RNAangiogenesisischemic strokemyeloid cellsoligodendrogenesisstroke therapy

Identifiers

PMID37307473
PMCPMC10288588
OpenAlexW4380354710

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.