Evidence map›Paper›PMID 38942014›Full record

ArticleCell2024

Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain.

Nicole Scott-Hewitt, Matthew Mahoney, Youtong Huang, Nils Korte, T Yvanka de Soysa, Daniel K Wilton, Emily Knorr, Kevin Mastro, Allison Chang, Allison Zhang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing 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

44 citing papers in PubMed.

  1. Article
  2. Review
  3. Microglia extract neuronal proteolytic organelles via skoupocytosis.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  10. Article
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  14. Article
  15. Review
  16. Review
  17. Article
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  19. Article
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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

14 authors.

Nicole Scott-HewittF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: nicole.scott-hewitt@childrens.harvard.edu.
Matthew MahoneyF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Youtong HuangF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nils KorteF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
T Yvanka de SoysaF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel K WiltonF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Emily KnorrF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Kevin MastroF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Allison ChangF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Allison ZhangF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
David MelvilleF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Monica SchenoneThe Broad Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christina HartiganThe Broad Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Beth StevensF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Investigator, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: beth.stevens@childrens.harvard.edu.

Funding

Regulation of Synaptic engulfment by human C4P50MH112491 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI Michael Craig Carroll, Beth Ann Stevens · 2017 to 2026
$29.5M
Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Supplement request for Training GrantT32NS007473 · NINDS · CHILDREN'S HOSPITAL BOSTON · PI Elizabeth C. Engle, Thomas L. Schwarz · 1999 to 2026
$6.9M
How do neurons in the brain decide to refine their synaptic connections in vivo?R01MH111647 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI Chinfei Chen, Hisashi Umemori · 2017 to 2026
$6.8M
Mechanisms of Activity-dependent Microglia-neuron Interactions in Development and DiseaseRF1NS092578 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI STEVENS, BETH ANN, UMEMORI, HISASHI · 2021 to 2023
$3.5M
NIA NIH HHS T32 AG000222NICHD NIH HHS P50 HD105351NIGMS NIH HHS T32 GM144273NIMH NIH HHS P50 MH112491NIMH NIH HHS R01 MH111647NINDS NIH HHS RF1 NS092578NINDS NIH HHS T32 NS007473
6 · The paper itself

Abstract

Neuroimmune interactions mediate intercellular communication and underlie critical brain functions. Microglia, CNS-resident macrophages, modulate the brain through direct physical interactions and the secretion of molecules. One such secreted factor, the complement protein C1q, contributes to complement-mediated synapse elimination in both developmental and disease models, yet brain C1q protein levels increase significantly throughout aging. Here, we report that C1q interacts with neuronal ribonucleoprotein (RNP) complexes in an age-dependent manner. Purified C1q protein undergoes RNA-dependent liquid-liquid phase separation (LLPS) in vitro, and the interaction of C1q with neuronal RNP complexes in vivo is dependent on RNA and endocytosis. Mice lacking C1q have age-specific alterations in neuronal protein synthesis in vivo and impaired fear memory extinction. Together, our findings reveal a biophysical property of C1q that underlies RNA- and age-dependent neuronal interactions and demonstrate a role of C1q in critical intracellular neuronal processes.

Indexed as

AgingBrainComplement C1qHomeostasisMicrogliaNeuronsRibonucleoproteinsAnimalsHumansMiceMice, Inbred C57BLComplement C1qRibonucleoproteinsC1qcomplementliquid-liquid phase separationmicroglianeuroimmuneneuronal translationpolysomeribonucleoprotein complexRNA-binding proteinRNA granule

Identifiers

PMID38942014
PMCPMC12344723

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.