Evidence map›Paper›PMID 31153962›Full record

ArticleNeuroscience2019

Programmed Epigenetic DNA Methylation-Mediated Reduced Neuroprogenitor Cell Proliferation and Differentiation in Small-for-Gestational-Age Offspring.

Mina Desai, Guang Han, Tie Li, Michael G Ross

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

Article in Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

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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

4 authors at 2 institutions in 1 country.

Mina DesaiPerinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: mdesai@labiomed.org.
Guang HanPerinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA.
Tie LiPerinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA.
Michael G RossPerinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, Charles R. Drew University, Los Angeles, CA, USA.
The Lundquist Institute · USHarbor–UCLA Medical Center · US

Funding

Mechanisms of Programmed Gestational HyperphagiaR01HD054751 · NICHD · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ROSS, MICHAEL GLENN · 2008 to 2012
$1.4M
Programmed Adipogenesis and Lipid DysregulationR01DK081756 · NIDDK · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI DESAI, MINA · 2010 to 2014
$1.4M
NICHD NIH HHS R01 HD054751NIDDK NIH HHS R01 DK081756
6 · The paper itself

Abstract

Small-for-gestational age (SGA) human newborns have an increased risk of hyperphagia and obesity, as well as a spectrum of neurologic and neurobehavioral abnormalities. We have shown that the SGA hypothalamic (appetite regulatory site) neuroprogenitor cells (NPCs) exhibit reduced proliferation and neuronal differentiation. DNA methylation (DNA methyltransferase; DNMT1) regulates neurogenesis by maintaining NPC proliferation and suppressing premature differentiation. Once differentiation ensues, DNMT1 preferentially promotes neuronal and inhibits astroglial fate. We hypothesized that the programmed dysfunction of NPC proliferation and differentiation in SGA offspring is epigenetically mediated via DNMT1. Pregnant rats received either ad libitum food (Control) or were 50% food-restricted to create SGA offspring. Primary hypothalamic NPCs from 1 day old SGA and Controls newborns were cultured and transfected with nonspecific or DNMT1-specific siRNA. NPC proliferation and protein expression of specific markers of NPC (nestin), neuroproliferative transcription factor (Hes1), neurons (Tuj1) and astrocytes (GFAP) were determined. Under basal conditions, SGA NPCs exhibited decreased DNMT1 and reduced proliferation and differentiation, as compared to Controls. In both SGA and Controls, DNMT1 siRNA in complete media inhibited NPC proliferation, consistent with reduced expression of nestin and Hes1. In differentiation media, DNMT1 siRNA decreased expression of Tuj1 but increased GFAP. In vivo data replicated these findings. In SGA offspring, impaired neurogenesis is epigenetically mediated, in part, via reduction in DNMT1 expression and suppression of Hes1 resulting in NPC differentiation. It is likely that the maturation of regions beyond the hypothalamus (e.g., cerebral cortex, hippocampus) may be impacted, contributing to poor cognitive and neurobehavioral competency in SGA offspring.

Indexed as

DNA MethylationAnimalsCell DifferentiationCell ProliferationFetal DevelopmentFetal Growth RetardationHypothalamusNeural Stem CellsNeurogenesisNeuronsRatsRats, Sprague-Dawleyastrocytesdevelopmental programmingDNMT1hypothalamusneurogenesisneurons

Identifiers

PMID31153962
PMCPMC8034830
OpenAlexW2947406197

What OpenQuestion holds

Textmetadata
LicenceTDM
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.