Evidence map›Paper›PMID 40336225›Full record

ArticleStem cells (Dayton, Ohio)2025

Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.

Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov and 2 more

Abstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Carlos Galicia AguirreBuck Institute for Research on Aging, Novato, CA 94945, United States.
Kizito-Tshitoko TshilengeBuck Institute for Research on Aging, Novato, CA 94945, United States.
Elena BattistoniBuck Institute for Research on Aging, Novato, CA 94945, United States.
Alejandro Lopez-RamirezBuck Institute for Research on Aging, Novato, CA 94945, United States.
Swati NaphadeBuck Institute for Research on Aging, Novato, CA 94945, United States.
Kevin PerezBuck Institute for Research on Aging, Novato, CA 94945, United States.
Akos A GerencserBuck Institute for Research on Aging, Novato, CA 94945, United States.ORCID 0000-0002-8052-3711
Sicheng SongDepartment of Biomedical Informatics and Medical Education, School of Medicine, University of Washington, Seattle, WA 98109, United States.
Sean D MooneyDepartment of Biomedical Informatics and Medical Education, School of Medicine, University of Washington, Seattle, WA 98109, United States.ORCID 0000-0003-2654-0833
Simon MelovBuck Institute for Research on Aging, Novato, CA 94945, United States.
Michelle E EhrlichDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Lisa M EllerbyBuck Institute for Research on Aging, Novato, CA 94945, United States.ORCID 0000-0002-9050-7977

Funding

Training in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8M
Identifying Factors Regulating Medium Spiny Neuron Differentiation or Maintenance as Therapeutic Targets for Huntington's Disease using Induced Pluripotent Stem CellsR01NS100529 · NINDS · BUCK INSTITUTE FOR RESEARCH ON AGING · PI Lisa M Ellerby · 2016 to 2026
$5.6M
Collaborative Center for X-linked Dystonia ParkinsonismNIA NIH HHS T32 AG000266NIH HHS R01-NS100529NINDS NIH HHS R01 NS100529The Taube Family Program in Regenerative Medicine Genome Editing for Huntington's Disease
6 · The paper itself

Abstract

Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene, resulting in a mutant HTT (mHTT) protein. Although mHTT is expressed in all tissues, it significantly affects medium spiny neurons (MSNs) in the striatum, resulting in their loss and the subsequent motor function impairment in HD. While HD symptoms typically emerge in midlife, disrupted MSN neurodevelopment is important. To explore the effects of mHTT on MSN development, we differentiated HD-induced pluripotent stem cells (iPSCs) and isogenic controls into neuronal stem cells, and then generated a developing MSN population encompassing early, intermediate progenitors, and nascent MSNs. Single-cell RNA sequencing revealed that the developmental trajectory of MSNs in our model closely emulated the trajectory of human fetal striatal neurons. However, in the HD MSN cultures, several crucial genes required for proper MSN maturation were downregulated, including members of the DLX family of transcription factors. Our analysis also uncovered a progressive dysregulation of multiple HD-related pathways as MSNs developed, including the NRF2-mediated oxidative stress response and mitogen-activated protein kinase signaling. Using the transcriptional profile of developing HD MSNs, we searched the L1000 dataset for small molecules that induce the opposite gene expression pattern. We pinpointed numerous small molecules with known benefits in HD models and previously untested novel molecules. A top candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways.

Indexed as

Corpus StriatumHuntington DiseaseNeuronsTranscriptomeCell DifferentiationHumansHuntingtin ProteinInduced Pluripotent Stem CellsMedium Spiny NeuronsHuntingtin ProteindevelopmentHuntington’s diseaseinduced pluripotent stem cellsmedium spiny neuronsneurodegenerationsingle-cell RNAseq

Identifiers

PMID40336225
PMCPMC12277964

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.