Evidence map›Paper›PMID 40804080›Full record

ArticleScientific reports2025

Lysosomal free sialic acid storage disorder iPSC-derived neural cells display altered glycosphingolipid metabolism.

Marya S Sabir, Vukasin M Jovanovic, Seungmi Ryu, Chaitali Sen, Pinar Ormanoglu, Laura Pollard, Richard Steet, William A Gahl, Marjan Huizing, Carlos A Tristan and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Marya S SabirUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Vukasin M JovanovicStem Cell Translation Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Seungmi RyuStem Cell Translation Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Chaitali SenStem Cell Translation Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Pinar OrmanogluStem Cell Translation Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Laura PollardGreenwood Genetic Center, Greenwood, SC, USA.
Richard SteetGreenwood Genetic Center, Greenwood, SC, USA.
William A GahlUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Marjan HuizingHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Carlos A TristanStem Cell Translation Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Frances M Platt *Department of Pharmacology, University of Oxford, Oxford, UK. frances.platt@pharm.ox.ac.uk.
May Christine V Malicdan *UDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. maychristine.malicdan@nih.gov.

Funding

Human Biochemical GeneticsZ01HG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM ALLEN · 2003 to 2008
$10.2M
Pathogenic Mechanisms of Lysosomal DiseaseR01NS128907 · NINDS · GREENWOOD GENETIC CENTER · PI STEET, RICHARD · 2022 to 2025
$1.2M
EXPANDING AND ENHANCING THE GENE EXPRESSION DATABASEF32HG000215 · NHGRI · JACKSON LABORATORY · PI CORRADI, JOHN P · 2000 to 2000
$10k
Intramural NIH HHS Z01 HG000215National Institutes of Health Intramural Research Program of the National Human Genome Research Institute HG-000215National Institutes of Health Oxford-Cambridge Scholars Program Graduate fellowship to MSSNHGRI NIH HHS F32 HG000215NINDS NIH HHS 5R01NS128907-17 to RSNINDS NIH HHS R01 NS128907Salla Treatment and Research Foundation Grant to LP
6 · The paper itself

Abstract

Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease caused by biallelic mutations in SLC17A5, encoding the lysosomal sialic acid exporter, SLC17A5 (sialin). While the involvement of oligodendroglia in FSASD pathogenesis is established, the roles of other neural cell types remain elusive. In this study, we utilized radial glial cells (iRGCs), immature and mature astrocytes (iIAs and iMAs, respectively), and cortical neurons (iCNs) differentiated from induced pluripotent stem cells (iPSCs) derived from two individuals with FSASD, alongside two independent healthy donors for comparison. We employed a multifaceted profiling approach, including the assessment of cellular glycosphingolipids (GSLs), transcriptomics focused on GSL metabolism genes, and 4-methylumbelliferone-based lysosomal enzyme activity measurements. Our findings revealed significant elevations in free sialic acid levels across all FSASD cell types, indicating that iPSCs and derived iRGCs, iIAs, iMAs and iCNs may be used to model FSASD in vitro. We observed significant alterations in the abundance of specific GSL species, predominantly in mature astrocytes, with fewer changes in other cell types. Transcriptomic analyses uncovered differential expression of genes involved in GSL catabolism, including those encoding glycohydrolases. Enzyme assays corroborated the transcriptomic findings, showing heightened glycohydrolase activities, particularly in mature astrocytes. Collectively, these data may help refine our understanding of neural cell phenotypes and potential contributors to selective vulnerability in FSASD.

Indexed as

GlycosphingolipidsInduced Pluripotent Stem CellsLysosomesNeuronsSialic Acid Storage DiseaseAstrocytesCell DifferentiationCells, CulturedHumansN-Acetylneuraminic AcidTranscriptomeGlycosphingolipidsN-Acetylneuraminic AcidAstrocytesGangliosidesGlycosphingolipidsSalla diseaseSialidaseSialin

Identifiers

PMID40804080
PMCPMC12350760

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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.