Evidence map›Paper›PMID 34050248›Full record

ArticleScientific reports2021

Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes.

Sureni V Mullegama, Steven D Klein, Stephen R Williams, Jeffrey W Innis, Frank J Probst, Chad Haldeman-Englert, Julian A Martinez-Agosto, Ying Yang, Yuchen Tian, Sarah H Elsea and 1 more

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

Article in Scientific reports, 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
1.4field-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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. A Novel Genetic Variant inInternational journal of molecular sciences · 2023
    Article
  5. Article
  6. Review
  7. Germline mosaicism in a family withCold Spring Harbor molecular case studies · 2022
    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

11 authors at 6 institutions in 1 country.

Sureni V MullegamaDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Steven D KleinDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Stephen R Williams10X Genomics, San Francisco, CA, USA.
Jeffrey W InnisDepartments of Human Genetics, Pediatrics and Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Frank J ProbstDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Chad Haldeman-EnglertMission Fullerton Genetics Center, Asheville, NC, 28803, USA.
Julian A Martinez-AgostoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Ying YangDepartment of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, 33612, USA.
Yuchen TianDivision of Animal Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA.
Sarah H ElseaDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. elsea@bcm.edu.
Toshihiko EzashiDivision of Animal Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA. ezashit@missouri.edu.
Baylor College of Medicine · USUniversity of California, Los Angeles · USUniversity of Missouri · US10X Genomics (United States) · USUniversity of Michigan–Ann Arbor · USUniversity of South Florida · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Understanding Repetitive Behavior in AutismP50HD055784 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOOKHEIMER, SUSAN Y · 2007 to 2021
$32.0M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NICHD NIH HHS P50 HD055784NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.

Indexed as

Abnormalities, MultipleAutism Spectrum DisorderAutistic DisorderCell DifferentiationChromosome DeletionChromosomes, Human, Pair 2Craniofacial AbnormalitiesDNA-Binding ProteinsGene ExpressionGene Expression ProfilingHumansInduced Pluripotent Stem CellsIntellectual DisabilityNeural Stem CellsNeurodevelopmental DisordersPhenotypeDNA-Binding ProteinsMBD5 protein, human

Identifiers

PMID34050248
PMCPMC8163803
OpenAlexW3165341275

What OpenQuestion holds

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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.