Evidence map›Paper›PMID 30699343›Full record

ArticleCell reports2019

REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease.

Katharina Meyer, Heather M Feldman, Tao Lu, Derek Drake, Elaine T Lim, King-Hwa Ling, Nicholas A Bishop, Ying Pan, Jinsoo Seo, Yuan-Ta Lin and 4 more

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

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 2 pooled it
11.4field-weighted citation impact, top 1% 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

135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.

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75 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 2 countries.

Katharina MeyerDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Heather M FeldmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Tao LuDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Derek DrakeDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Elaine T LimDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
King-Hwa LingDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Nicholas A BishopDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Ying PanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jinsoo SeoThe Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Yuan-Ta LinThe Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Susan C SuThe Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Li-Huei TsaiThe Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Bruce A YanknerDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bruce_yankner@hms.harvard.edu.
Harvard University · USMassachusetts Institute of Technology · USUniversiti Putra Malaysia · MY

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Targeting a Novel Regulator of Brain Aging and Alzheimer's Disease (ADMINISTRATIVE SUPPLEMENT- SAGE)R01AG046174 · NIA · HARVARD MEDICAL SCHOOL · PI TSAI, LI-HUEI, YANKNER, BRUCE A · 2014 to 2018
$4.9M
Exploring a Novel Paradigm of Schizophrenia and Bipolar DisorderR01MH113279 · NIMH · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M, YANKNER, BRUCE A · 2016 to 2020
$4.7M
Alzheimer's Disease Risk Genes in Human Microglia and Neurons Derived from iPSCsRF1AG048029 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2014 to 2014
$2.1M
Genome Engineering an IPSC Model of Alzheimer's DiseaseRF1AG048056 · NIA · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M, YANKNER, BRUCE A · 2014 to 2014
$2.1M
Modeling the Aging EpigenomeDP1OD006849 · OD · HARVARD MEDICAL SCHOOL · PI YANKNER, BRUCE A · 2010 to 2011
$1.7M
NHGRI NIH HHS RM1 HG008525NIA NIH HHS R01 AG046174NIA NIH HHS RF1 AG048029NIA NIH HHS RF1 AG048056NIH HHS DP1 OD006849NIMH NIH HHS R01 MH113279
6 · The paper itself

Abstract

The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.

Indexed as

Gene Regulatory NetworksAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins ECell DifferentiationCellular ReprogrammingFibroblastsGene Expression RegulationHumansInduced Pluripotent Stem CellsMiddle AgedNeural Stem CellsNeurogenesisNeuronsAmyloid beta-PeptidesApolipoproteins ERE1-Silencing Transcription FactorRepressor ProteinsAlzheimer’s diseaseapolipoprotein Eepigeneticinduced pluripotent stem cellneural differentiationneural progenitorneurogenesisorganoidpolycombREST

Identifiers

PMID30699343
PMCPMC6386196
OpenAlexW2913604250

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.