Evidence mapPaperPMID 37516746Full record

ArticleCommunications biology2023

An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis.

Karo Talvio, Victoria A Wagner, Rimante Minkeviciene, Jay S Kirkwood, Anna O Kulinich, Juzoh Umemori, Anil Bhatia, Manhoi Hur, Reijo Käkelä, Iryna M Ethell and 1 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Astrocytes in fragile X syndrome.Frontiers in cellular neuroscience · 2023
    Review
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

11 authors at 3 institutions in 2 countries.

Karo TalvioDepartment of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Victoria A WagnerDivision of Biomedical Sciences, and Neuroscience Graduate Program, School of Medicine, University of California Riverside, Riverside, CA, USA.ORCID 0000-0002-8370-9669
Rimante MinkevicieneDepartment of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Jay S KirkwoodMetabolomics Core Facility, Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA.
Anna O KulinichDivision of Biomedical Sciences, and Neuroscience Graduate Program, School of Medicine, University of California Riverside, Riverside, CA, USA.
Juzoh UmemoriGene and Cell Technology, A.I.Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
Anil BhatiaMetabolomics Core Facility, Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA.
Manhoi HurMetabolomics Core Facility, Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA.ORCID 0000-0003-4278-3210
Reijo KäkeläHelsinki University Lipidomics Unit, HiLIPID, Helsinki Institute of Life Science, HiLIFE, Biocenter Finland (Metabolomics), and Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-4953-3062
Iryna M EthellDivision of Biomedical Sciences, and Neuroscience Graduate Program, School of Medicine, University of California Riverside, Riverside, CA, USA.ORCID 0000-0002-1324-6611
Maija L CastrénDepartment of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. maija.castren@helsinki.fi.ORCID 0000-0002-9644-5295
University of California, Riverside · USUniversity of Helsinki · FIUniversity of Eastern Finland · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesterol is an essential membrane structural component and steroid hormone precursor, and is involved in numerous signaling processes. Astrocytes regulate brain cholesterol homeostasis and they supply cholesterol to the needs of neurons. ATP-binding cassette transporter A1 (ABCA1) is the main cholesterol efflux transporter in astrocytes. Here we show dysregulated cholesterol homeostasis in astrocytes generated from human induced pluripotent stem cells (iPSCs) derived from males with fragile X syndrome (FXS), which is the most common cause of inherited intellectual disability. ABCA1 levels are reduced in FXS human and mouse astrocytes when compared with controls. Accumulation of cholesterol associates with increased desmosterol and polyunsaturated phospholipids in the lipidome of FXS mouse astrocytes. Abnormal astrocytic responses to cytokine exposure together with altered anti-inflammatory and cytokine profiles of human FXS astrocyte secretome suggest contribution of inflammatory factors to altered cholesterol homeostasis. Our results demonstrate changes of astrocytic lipid metabolism, which can critically regulate membrane properties and affect cholesterol transport in FXS astrocytes, providing target for therapy in FXS.

Indexed as

Fragile X SyndromeInduced Pluripotent Stem CellsAnimalsAstrocytesCytokinesHomeostasisHumansLipid MetabolismMaleMiceCytokines

Identifiers

PMID37516746
PMCPMC10387075
OpenAlexW4385380125

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.