Evidence map›Paper›PMID 35672450›Full record

ArticleExperimental & molecular medicine2022

ARID1B, a molecular suppressor of erythropoiesis, is essential for the prevention of Monge's disease.

Priti Azad, Andrew B Caldwell, Srinivasan Ramachandran, Nathanael J Spann, Ali Akbari, Francisco C Villafuerte, Daniela Bermudez, Helen Zhao, Orit Poulsen, Dan Zhou and 3 more

Open access · goldAbstract read
In one paragraph

Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 17% 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, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Key GenesGenes · 2024
    Article
  7. Altitude illnesses.Nature reviews. Disease primers · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. 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

13 authors at 3 institutions in 2 countries.

Priti AzadDivision of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Andrew B Caldwell *Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Srinivasan Ramachandran *Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Nathanael J SpannDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Ali AkbariDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Francisco C VillafuerteLaboratorio de Fisiología del Transporte de Oxigeno/Fisiología Comparada, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, 31, Peru.
Daniela BermudezLaboratorio de Fisiología del Transporte de Oxigeno/Fisiología Comparada, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, 31, Peru.
Helen ZhaoDivision of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Orit PoulsenDivision of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Dan ZhouDivision of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Vineet BafnaDepartment of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.
Shankar SubramaniamDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Gabriel G HaddadDivision of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. ghaddad@health.ucsd.edu.
University of California, San Diego · USUniversidad Peruana Cayetano Heredia · PEBroad Institute · US

Funding

Computational methods for detecting patterns of complex genomic variationR01GM114362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2016 to 2026
$3.1M
Molecular Basis of Hypoxia-Induced Excessive ErythrocytosisR01HL146530 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HADDAD, GABRIEL G · 2019 to 2022
$2.4M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NHLBI NIH HHS R01 HL146530NIGMS NIH HHS R01 GM114362NIH HHS S10 OD026929
6 · The paper itself

Abstract

At high altitude Andean region, hypoxia-induced excessive erythrocytosis (EE) is the defining feature of Monge's disease or chronic mountain sickness (CMS). At the same altitude, resides a population that has developed adaptive mechanism(s) to constrain this hypoxic response (non-CMS). In this study, we utilized an in vitro induced pluripotent stem cell model system to study both populations using genomic and molecular approaches. Our whole genome analysis of the two groups identified differential SNPs between the CMS and non-CMS subjects in the ARID1B region. Under hypoxia, the expression levels of ARID1B significantly increased in the non-CMS cells but decreased in the CMS cells. At the molecular level, ARID1B knockdown (KD) in non-CMS cells increased the levels of the transcriptional regulator GATA1 by 3-fold and RBC levels by 100-fold under hypoxia. ARID1B KD in non-CMS cells led to increased proliferation and EPO sensitivity by lowering p53 levels and decreasing apoptosis through GATA1 mediation. Interestingly, under hypoxia ARID1B showed an epigenetic role, altering the chromatin states of erythroid genes. Indeed, combined Real-time PCR and ATAC-Seq results showed that ARID1B modulates the expression of GATA1 and p53 and chromatin accessibility at GATA1/p53 target genes. We conclude that ARID1B is a novel erythroid regulator under hypoxia that controls various aspects of erythropoiesis in high-altitude dwellers.

Indexed as

Altitude SicknessDNA-Binding ProteinsTranscription FactorsChromatinChronic DiseaseErythropoiesisHumansHypoxiaTumor Suppressor Protein p53ARID1B protein, humanChromatinDNA-Binding ProteinsTranscription FactorsTumor Suppressor Protein p53

Identifiers

PMID35672450
PMCPMC9256584
OpenAlexW4281786081

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.