Evidence map›Paper›PMID 36993714›Full record

ArticlebioRxiv : the preprint server for biology2023

Manipulation of the nucleoscaffold potentiates cellular reprogramming kinetics.

Benjamin A Yang, André Monteiro da Rocha, Isabel Newton, Anna Shcherbina, Sing-Wan Wong, Paula M Fraczek, Jacqueline A Larouche, Harrison L Hiraki, Brendon M Baker, Jae-Won Shin and 3 more

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

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Benjamin A YangDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
André Monteiro da RochaDept. of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Isabel NewtonDept. of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Anna ShcherbinaDept. of Biomedical Informatics, Stanford University, Palo Alto, CA 94305, USA.
Sing-Wan WongDept. of Pharmacology and Biomedical Engineering, University of Illinois at Chicago, Chicago, IL 60612, USA.
Paula M FraczekDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Jacqueline A LaroucheDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Harrison L HirakiDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Brendon M BakerDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Jae-Won ShinDept. of Pharmacology and Biomedical Engineering, University of Illinois at Chicago, Chicago, IL 60612, USA.
Shuichi TakayamaWallace Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
M D ThoulessDept. of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Carlos A AguilarDept. of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
University of Michigan · USUniversity of Illinois Chicago · USGeorgia Institute of Technology · USPalo Alto University · US

Funding

Research Education CoreP30AG024824 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Neil Alexander · 2004 to 2026
$29.2M
Structure, Composition, & Histology Core - Core BP30AR069620 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARL J JEPSEN · 2016 to 2026
$8.4M
Microfluidics in Biomedical Sciences Training ProgramT32EB005582 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FAN, XUDONG · 2005 to 2020
$3.9M
Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosisR01HL141255 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHIN, JAE-WON · 2019 to 2023
$2.0M
Engineering microscale hydrogel deposition to direct single stem cell differentiationR01GM141147 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHIN, JAE-WON · 2021 to 2024
$1.9M
Super-resolution visualization of histones and histone modifications on individual chromatin fibersR01GM123517 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI LIU, YIFAN, TAKAYAMA, SHUICHI · 2017 to 2020
$1.6M
NHLBI NIH HHS R01 HL141255NIAMS NIH HHS P30 AR069620NIA NIH HHS P30 AG024824NIBIB NIH HHS T32 EB005582NIGMS NIH HHS R01 GM123517NIGMS NIH HHS R01 GM141147
6 · The paper itself

Abstract

Somatic cell fate is an outcome set by the activities of specific transcription factors and the chromatin landscape and is maintained by gene silencing of alternate cell fates through physical interactions with the nuclear scaffold. Here, we evaluate the role of the nuclear scaffold as a guardian of cell fate in human fibroblasts by comparing the effects of transient loss (knockdown) and mutation (progeria) of functional Lamin A/C, a core component of the nuclear scaffold. We observed that Lamin A/C deficiency or mutation disrupts nuclear morphology, heterochromatin levels, and increases access to DNA in lamina-associated domains. Changes in Lamin A/C were also found to impact the mechanical properties of the nucleus when measured by a microfluidic cellular squeezing device. We also show that transient loss of Lamin A/C accelerates the kinetics of cellular reprogramming to pluripotency through opening of previously silenced heterochromatin domains while genetic mutation of Lamin A/C into progerin induces a senescent phenotype that inhibits the induction of reprogramming genes. Our results highlight the physical role of the nuclear scaffold in safeguarding cellular fate.

Identifiers

PMID36993714
PMCPMC10055010
OpenAlexW4324028346

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.