Evidence map›Paper›PMID 34995493›Full record

ArticleCell stem cell2022

Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors.

Hiruy S Meharena, Asaf Marco, Vishnu Dileep, Elana R Lockshin, Grace Y Akatsu, James Mullahoo, L Ashley Watson, Tak Ko, Lindsey N Guerin, Fatema Abdurrob and 4 more

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

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
10.1field-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

66 citing papers in PubMed, 97 citations in OpenAlex.

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6 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 2 institutions in 1 country.

Hiruy S MeharenaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: hiruym@mit.edu.
Asaf MarcoPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Vishnu DileepPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Elana R LockshinPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Grace Y AkatsuPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
James MullahooBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
L Ashley WatsonPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Tak KoPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Lindsey N GuerinPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Fatema AbdurrobPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shruthi RengarajanPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Malvina PapanastasiouBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jacob D JaffeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Li-Huei TsaiPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: lhtsai@mit.edu.
Massachusetts Institute of Technology · USBroad Institute · US

Funding

There and Back Again: Epigenetic Reinforcement of Cellular Signaling States - OverallU54HG008097 · NHGRI · BROAD INSTITUTE, INC. · PI JAFFE, JACOB DAVID · 2014 to 2019
$9.3M
Nuclear-Metabolic Interplay in Down syndromeR01HD115635 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Hiruy Sibhatu Meharena · 2024 to 2026
$2.0M
NHGRI NIH HHS U54 HG008097NICHD NIH HHS R01 HD115635
6 · The paper itself

Abstract

Down syndrome (DS) is a genetic disorder driven by the triplication of chromosome 21 (T21) and characterized by a wide range of neurodevelopmental and physical disabilities. Transcriptomic analysis of tissue samples from individuals with DS has revealed that T21 induces a genome-wide transcriptional disruption. However, the consequences of T21 on the nuclear architecture and its interplay with the transcriptome remain unknown. In this study, we find that unlike human induced pluripotent stem cells (iPSCs), iPSC-derived neural progenitor cells (NPCs) exhibit genome-wide "chromosomal introversion," disruption of lamina-associated domains, and global chromatin accessibility changes in response to T21, consistent with the transcriptional and nuclear architecture changes characteristic of senescent cells. Treatment of T21-harboring NPCs with senolytic drugs alleviates the transcriptional, molecular, and cellular dysfunctions associated with DS. Our findings provide a mechanistic link between T21 and global transcriptional disruption and indicate that senescence-associated phenotypes may play a key role in the neurodevelopmental pathogenesis of DS.

Indexed as

Down SyndromeInduced Pluripotent Stem CellsNeural Stem CellsGene Expression ProfilingHumansTranscriptome3D-genomeaneuploidyATAC-seqDown syndromeepigenomeHi-Clamina-associated domains (LADs)RNA-seqsenescencesenolytic drugstranscriptome

Identifiers

PMID34995493
PMCPMC8805993
OpenAlexW4205519160

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.