Evidence map›Paper›PMID 20650959›Full record

ArticleHuman molecular genetics2010

Centromere protein A dynamics in human pluripotent stem cell self-renewal, differentiation and DNA damage.

Gayane Ambartsumyan, Rajbir K Gill, Silvia Diaz Perez, Deirdre Conway, John Vincent, Yamini Dalal, Amander T Clark

Abstract read
In one paragraph

Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

19 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Mitotic drive in asymmetric epigenetic inheritance.Biochemical Society transactions · 2022
    Article
  3. Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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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

7 authors at 3 institutions in 2 countries.

Gayane AmbartsumyanDepartment of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Rajbir K Gill
Silvia Diaz Perez
Deirdre Conway
John Vincent
Yamini Dalal
Amander T Clark
University of California, Los Angeles · USInstitute of Molecular and Cell Biology · RUNational Cancer Institute · US

Funding

Human Embryonic Stem Cell CoreP01GM081621 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2008 to 2012
$9.3M
Biomechanical properties of chromatin in cancer and normal cellsZIABC011207 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DALAL, YAMINI P · 2009 to 2025
$8.8M
Understanding Epigenetic Remodeling in Primordial Germ CellsR01HD058047 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLARK, AMANDER · 2009 to 2023
$5.6M
Kinetochore Interaction with Centromere Chromatin in human cellsZIABC011209 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DALAL, YAMINI P · 2009 to 2025
$5.5M
WOMEN'S REPRODUCTIVE HEALTH RESEARCH CAREER DEVELOPMENTK12HD001281 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHAUDHURI, GAUTAM · 1998 to 2008
$2.8M
Intramural NIH HHS ZIA BC011207NICHD NIH HHS 5 K12 HD001281NICHD NIH HHS R01 1R01HD058047-01NIGMS NIH HHS P01 P01GM081621
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) hold significant promise for use in regenerative medicine, or as a model to understand human embryo development. However, the basic mechanisms required for proliferation and self-renewal of hPSCs have not been fully uncovered. Proliferation in all eukaryotes is dependent upon highly regulated expression of the histone H3 variant Centromere protein A (CENP-A). In the current study, we demonstrate that hPSCs have a unique messenger ribonucleic acid (mRNA) reserve of CENP-A not found in somatic fibroblasts. Using short hairpin RNA technology to reduce but not ablate CENP-A, we show that CENP-A-depleted hPSCs are still capable of maintaining a functional centromeric mark, whereas fibroblasts are not. However, upon induction of differentiation or DNA damage, hPSCs with depleted CENP-A arrest in G2/M and undergo apoptosis. Analysis of CENP-A dynamics following DNA damage in hPSCs reveals that 60 min after irradiation, CENP-A is found in multiple small nuclear foci that are mutually exclusive to γH2AX as well as CENP-C. Furthermore, following irradiation, hPSCs with depleted CENP-A mount a normal apoptotic response at 6 h; however at 24 h, apoptosis is significantly increased in CENP-A-depleted hPSCs relative to control. Taken together, our results indicate that hPSCs exhibit a unique mechanism for maintaining genomic integrity by possessing the flexibility to reduce the amount of CENP-A required to maintain a functional centromere under self-renewing conditions, and maintaining a reserve of CENP-A mRNA to rebuild the centromere following differentiation or DNA damage.

Indexed as

DNA DamageApoptosisAutoantigensBlotting, WesternCentromereCentromere Protein AChromosomal Proteins, Non-HistoneDNA-Binding ProteinsFibroblastsFlow CytometryFluorescent Antibody TechniqueG2 PhaseGene Expression RegulationHistonesHumansPluripotent Stem CellsAutoantigensCENPA protein, humanCentromere Protein AChromosomal Proteins, Non-HistoneDNA-Binding ProteinsHistonesRNA, MessengerRNA, Small Interfering

Identifiers

PMID20650959
PMCPMC2947403
OpenAlexW2114175147

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.