Evidence map›Paper›PMID 37214832›Full record

ArticlebioRxiv : the preprint server for biology2023

Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias.

Luke C Bartelt, Pawel M Switonski, Grażyna Adamek, Juliana Carvalho, Lisa A Duvick, Sabrina I Jarrah, Hayley S McLoughlin, Daniel R Scoles, Stefan M Pulst, Harry T Orr and 3 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 7 citations in OpenAlex.

No citing paper in PubMed yet.

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

13 authors at 7 institutions in 2 countries.

Luke C BarteltUniversity Program in Genetics & Genomics, Duke University Medical Center, Durham, NC 27710, USA.
Pawel M SwitonskiDepartment of Medical Biotechnology, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland.
Grażyna AdamekDepartment of Medical Biotechnology, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland.
Juliana CarvalhoDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Lisa A DuvickInstitute for Translational Neuroscience, and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Sabrina I JarrahDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Hayley S McLoughlinDepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Daniel R ScolesDepartment of Neurology, University of Utah, Salt Lake City, UT 84132, USA.
Stefan M PulstDepartment of Neurology, University of Utah, Salt Lake City, UT 84132, USA.
Harry T OrrInstitute for Translational Neuroscience, and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Court HullDepartment of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
Craig B LoweDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Albert R La SpadaDepartments of Pathology & Laboratory Medicine, Neurology, Biological Chemistry, and Neurobiology & Behavior, University of California, Irvine; Irvine, CA 92697, USA.
Duke Medical Center · USInstitute of Bioorganic Chemistry, Polish Academy of Sciences · PLIrvine Valley College · USUniversity of Michigan · USUniversity of Minnesota · USUniversity of Utah · USDuke University · US

Funding

SCA7 RETINAL DEGENERATION: MOLECULAR BASIS &THERAPYR01EY014061 · NEI · UNIVERSITY OF WASHINGTON · PI ALBERT R LA SPADA · 2002 to 2026
$8.4M
La Spada Outstanding Investigator AwardR35NS122140 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ALBERT R LA SPADA · 2021 to 2026
$7.2M
Ataxin-2 complex proteins in neurodegeneration.R35NS127253 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stefan M. PULST · 2022 to 2026
$4.6M
Molecular genetics of neurodegenerative pathogenic and protective pathways: The SCA1 perspectiveR35NS127248 · NINDS · UNIVERSITY OF MINNESOTA · PI Harry T. Orr · 2022 to 2026
$3.9M
Spinocerebellar Ataxia Type 2 Gene and Gene ProductR37NS033123 · NINDS · UNIVERSITY OF UTAH · PI PULST, STEFAN M. · 2014 to 2020
$3.6M
RNA Granules in Cerebellar NeurodegenerationR01NS097903 · NINDS · UNIVERSITY OF UTAH · PI SCOLES, DANIEL R · 2017 to 2021
$2.7M
NEI NIH HHS R01 EY014061NINDS NIH HHS R01 NS097903NINDS NIH HHS R35 NS122140NINDS NIH HHS R35 NS127248NINDS NIH HHS R35 NS127253NINDS NIH HHS R37 NS033123
6 · The paper itself

Abstract

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. SCA7 patients display a striking loss of Purkinje cell (PC) neurons with disease progression; however, PCs are rare, making them difficult to characterize. We developed a PC nuclei enrichment protocol and applied it to single-nucleus RNA-seq of a SCA7 knock-in mouse model. Our results unify prior observations into a central mechanism of cell identity loss, impacting both glia and PCs, driving accumulation of inhibitory synapses and altered PC spiking. Zebrin-II subtype dysregulation is the predominant signal in PCs, leading to complete loss of zebrin-II striping at motor symptom onset in SCA7 mice. We show this zebrin-II subtype degradation is shared across Polyglutamine Ataxia mouse models and SCA7 patients. It has been speculated that PC subtype organization is critical for cerebellar function, and our results suggest that a breakdown of zebrin-II parasagittal striping is pathological.

Identifiers

PMID37214832
PMCPMC10197555
OpenAlexW4327967424

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.