Evidence map›Paper›PMID 38906887›Full record

ArticleNature communications2024

Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice.

Alicia Bedolla, Elliot Wegman, Max Weed, Messiyah K Stevens, Kierra Ware, Aditi Paranjpe, Anastasia Alkhimovitch, Igal Ifergan, Aleksandr Taranov, Joshua D Peter and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

49 citing papers in PubMed.

  1. Article
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  8. Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026
    Article
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  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Microglial HVCN1 Deficiency Improves Movement and Survival of SOD1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Alicia BedollaDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.
Elliot WegmanDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.
Max WeedDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.ORCID http://orcid.org/0009-0003-9190-3626
Messiyah K StevensDepartment of Psychology, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-8653-0269
Kierra WareDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0001-6947-2514
Aditi ParanjpeInformation Services for Research, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
Anastasia AlkhimovitchDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.
Igal IferganDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.
Aleksandr TaranovDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0001-5508-6671
Joshua D PeterDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-0943-9955
Rosa Maria Salazar GonzalezDivision of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
J Elliott RobinsonDivision of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0001-9417-3938
Lucas McClainDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA.
Krishna M RoskinDivision of Immunobiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-5864-5093
Nigel H GreigTranslational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Yu LuoDepartment of Molecular and Cellular Biosciences, University of Cincinnati, Cincinnati, OH, USA. luoy2@ucmail.uc.edu.ORCID http://orcid.org/0000-0002-7939-5505

Funding

Design And Development Of Experimental Therapeutics ((Systemic & Neurodegenerative Disorders and Alzheimer's Disease)ZIAAG000311 · NIA · NATIONAL INSTITUTE ON AGING · PI GREIG, NIGEL H. · 2009 to 2025
$16.0M
ENVIRONMETAL CARCINOGENESIS AND MUTAGENESIST32ES007250 · NIEHS · UNIVERSITY OF CINCINNATI · PI MILLER, WILLIAM E · 1988 to 2024
$11.9M
PREDOCTORAL TRAINING PROGRAM IN THE NEUROSCIENCEST32NS007453 · NINDS · UNIVERSITY OF CINCINNATI · PI HERMAN, JAMES P · 1997 to 2025
$4.0M
Investigating the role of CSF production and circulation in aging and Alzheimer's diseaseR01AG083164 · NIA · UNIVERSITY OF CINCINNATI · PI Yu Luo · 2023 to 2026
$2.6M
The role TGF-beta Signaling pathway in microglia and astrocytes homeostasis and cellular interactionsR01NS125074 · NINDS · UNIVERSITY OF CINCINNATI · PI Yu Luo · 2022 to 2026
$2.6M
Role of the neurovascular molecule Wnt in regulating CNS inflammatory responsesR35GM146890 · NIGMS · UNIVERSITY OF CINCINNATI · PI Igal Ifergan · 2022 to 2026
$2.2M
Leica Stellaris 8 Confocal MicroscopeS10OD030402 · OD · UNIVERSITY OF CINCINNATI · PI HONG, CHRISTIAN I · 2021 to 2021
$598k
Ablating choroid plexus epithelial cells in the developing mouse brain: A new tool to approach CSF disordersR21NS127177 · NINDS · UNIVERSITY OF CINCINNATI · PI GOTO, JUNE, LUO, YU · 2022 to 2022
$457k
A Dual Role of Activin-like kinase 5 (ALK5)-mediated TGF Beta Signaling in Adult NeurogenesisF31NS129204 · NINDS · UNIVERSITY OF CINCINNATI · PI WARE, KIERRA · 2023 to 2025
$83k
The Role of Activin-like kinase 5 (ALK5) for maintaining microglia and astrocyte homeostasis and activationF31NS125930 · NINDS · UNIVERSITY OF CINCINNATI · PI BEDOLLA, ALICIA MARIE · 2022 to 2023
$80k
NIA NIH HHS R01 AG083164NIEHS NIH HHS T32 ES007250NIGMS NIH HHS R35 GM146890NIH HHS S10 OD030402NINDS NIH HHS F31 NS125930NINDS NIH HHS F31 NS129204NINDS NIH HHS R01 NS125074NINDS NIH HHS R21 NS127177NINDS NIH HHS T32 NS007453Simons Foundation 663007U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 1F31NS125930U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS125074U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R21NS127177U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R35GM146890U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG083164
6 · The paper itself

Abstract

While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.

Indexed as

Autocrine CommunicationCognitionHomeostasisMice, KnockoutMicrogliaTransforming Growth Factor beta1AnimalsAstrocytesBrainMaleMiceMice, Inbred C57BLNeuronsSignal TransductionTranscriptomeTgfb1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID38906887
PMCPMC11192737

What OpenQuestion holds

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Registered trials

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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.