Evidence map›Paper›PMID 33611676›Full record

ArticleJournal of assisted reproduction and genetics2021

CAG repeat instability in embryonic stem cells and derivative spermatogenic cells of transgenic Huntington's disease monkey.

Sujittra Khampang, Rangsun Parnpai, Wiriya Mahikul, Charles A Easley, In Ki Cho, Anthony W S Chan

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

Article in Journal of assisted reproduction and genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Application of the transgenic pig model in biomedical research: A review.Frontiers in cell and developmental biology · 2022
    Review
  7. 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

6 authors at 5 institutions in 3 countries.

Sujittra KhampangDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
Rangsun ParnpaiEmbryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
Wiriya MahikulFaculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.
Charles A EasleyDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA.
In Ki ChoDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA. inkicho@outlook.com.
Anthony W S ChanDivision of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA. awschan@hotmail.com.ORCID http://orcid.org/0000-0002-4388-2280
Emory University · USChulabhorn Hospital · THEmory National Primate Research CenterSuranaree University of Technology · THUniversity of Georgia · US

Funding

Transgenic Huntington's disease monkey resourceR24OD010930 · OD · EMORY UNIVERSITY · PI CHAN, ANTHONY WING SANG · 2012 to 2018
$6.1M
N-terminal huntingtin and Huntington disease neuropathologyR01NS101701 · NINDS · EMORY UNIVERSITY · PI ESCAYG, ANDREW P · 2017 to 2021
$2.2M
Using Non-Human Primate Pluripotent Stem Cells to Treat Male-Factor InfertilityR21OD020182 · OD · EMORY UNIVERSITY · PI CHAN, ANTHONY WING SANG, EASLEY, CHARLES A. · 2015 to 2016
$486k
NIH HHS NS101701NIH HHS OD010930NIH HHS OD020182NIH HHS R21 OD020182NIH HHS R24 OD010930NINDS NIH HHS R01 NS101701
6 · The paper itself

Abstract

purposeThe expansion of CAG (glutamine; Q) trinucleotide repeats (TNRs) predominantly occurs through male lineage in Huntington's disease (HD). As a result, offspring will have larger CAG repeats compared to their fathers, which causes an earlier onset of the disease called genetic anticipation. This study aims to develop a novel in vitro model to replicate CAG repeat instability in early spermatogenesis and demonstrate the biological process of genetic anticipation by using the HD stem cell model for the first time.

methodsHD rhesus monkey embryonic stem cells (rESCs) were cultured in vitro for an extended period. Male rESCs were used to derive spermatogenic cells in vitro with a 10-day differentiation. The assessment of CAG repeat instability was performed by GeneScan and curve fit analysis.

resultsSpermatogenic cells derived from rESCs exhibit progressive expansion of CAG repeats with high daily expansion rates compared to the extended culture of rESCs. The expansion of CAG repeats is cell type-specific and size-dependent.

conclusionsHere, we report a novel stem cell model that replicates genome instability and CAG repeat expansion in in vitro derived HD monkey spermatogenic cells. The in vitro spermatogenic cell model opens a new opportunity for studying TNR instability and the underlying mechanism of genetic anticipation, not only in HD but also in other TNR diseases.

Indexed as

Adult Germline Stem CellsAnimalsAnimals, Genetically ModifiedCell DifferentiationDisease Models, AnimalEmbryonic Stem CellsGenomic InstabilityHumansHuntington DiseaseMacaca mulattaMaleMicrosatellite InstabilityTrinucleotide RepeatsCAG repeat instabilityGenetic anticipationHD rhesus monkey embryonic stem cells (rESCs)Huntington’s diseaseSpermatogenic cells

Identifiers

PMID33611676
PMCPMC8190423
OpenAlexW3129508462

What OpenQuestion holds

Textmetadata
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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.