Evidence map›Paper›PMID 31273310›Full record

ArticleScientific reports2019

Engineering a humanized telomerase reverse transcriptase gene in mouse embryonic stem cells.

De Cheng, Yuanjun Zhao, Fan Zhang, Jinglong Zhang, Shuwen Wang, Jiyue Zhu

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Telomere dysfunction in Tert knockout mice delays BrafInternational journal of cancer · 2024
    Article
  5. Humanization of the mouseResearch square · 2024
    Article
  6. Review
  7. Review
  8. Article
  9. Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

De ChengDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, Washington, USA.ORCID http://orcid.org/0000-0003-3712-6232
Yuanjun ZhaoDepartment of C & M Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Fan ZhangDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, Washington, USA.ORCID http://orcid.org/0000-0002-7186-6317
Jinglong ZhangDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, Washington, USA.
Shuwen WangDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, Washington, USA.
Jiyue ZhuDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, Washington, USA. jiyue.zhu@wsu.edu.
Washington State University Spokane · USPennsylvania State University · US

Funding

Repression of the hTERT gene during cell differentiation: Administrative Supplement for EquipmentR01GM071725 · NIGMS · WASHINGTON STATE UNIVERSITY · PI ZHU, JIYUE · 2004 to 2020
$4.2M
Development of mouse strains with human-like telomerase regulationR21OD021432 · OD · WASHINGTON STATE UNIVERSITY · PI ZHU, JIYUE · 2015 to 2016
$401k
NIGMS NIH HHS R01 GM071725NIH HHS R21 OD021432U.S. Department of Health & Human Services | National Institutes of Health (NIH) R21OD021432U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM071725
6 · The paper itself

Abstract

Telomerase is expressed in adult mouse, but not in most human, tissues and mouse telomeres are much longer than those in humans. This interspecies difference of telomere homeostasis poses a challenge in modeling human diseases using laboratory mice. Using chromatinized bacterial artificial chromosome reporters, we discovered that the 5' intergenic region, introns 2 and 6 of human telomerase gene (hTERT) were critical for regulating its promoter in somatic cells. Accordingly, we engineered a humanized gene, hmTert, by knocking-in a 47-kilobase hybrid fragment containing these human non-coding sequences into the mTert locus in mouse embryonic stem cells (mESCs). The hmTert gene, encoding the wildtype mTert protein, was fully functional, as a mESC line with homozygous hmTert alleles proliferated for over 400 population doublings without exhibiting chromosomal abnormalities. Like human ESCs, the engineered mESCs contained high telomerase activity, which was repressed upon their differentiation into fibroblast-like cells in a histone deacetylase-dependent manner. Fibroblast-like cells differentiated from these mESCs contained little telomerase activity. Thus, telomerase in mESCs with the hmTert alleles was subjected to human-like regulation. Our study revealed a novel approach to engineer a humanized telomerase gene in mice, achieving a milestone in creating a mouse model with humanized telomere homeostasis.

Indexed as

Genetic EngineeringAnimalsCell DifferentiationFibroblastsGenomeHuman Embryonic Stem CellsHumansMiceMouse Embryonic Stem CellsPromoter Regions, GeneticTelomeraseTelomereTelomere HomeostasisTelomerase

Identifiers

PMID31273310
PMCPMC6609615
OpenAlexW2955090598

What OpenQuestion 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 OpenQuestion graph.