Evidence map›Paper›PMID 38354231›Full record

ArticleScience advances2024

Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming.

Yang Song, Jennifer Soto, Sze Yue Wong, Yifan Wu, Tyler Hoffman, Navied Akhtar, Sam Norris, Julia Chu, Hyungju Park, Douglas O Kelkhoff and 6 more

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

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
10.4field-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

29 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Mechanical regulation of cell memory.Nature structural & molecular biology · 2026
    Review
  6. Review
  7. Review
  8. Physiomimetic culture bias durotaxis toward soft environments.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. Mechanomedicine.Nature reviews bioengineering · 2026
    Article
  12. Review
  13. Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Chemical compensation to mechanical loss in cell mechanosensation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Article
  20. Review
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

16 authors at 6 institutions in 4 countries.

Yang SongDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID 0000-0001-8026-9293
Jennifer SotoDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Sze Yue WongDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
Yifan WuDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Tyler HoffmanDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Navied AkhtarDepartment of Biomedical Engineering, University of California, Irvine, Irvine, CA 92617, USA.
Sam NorrisDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Julia ChuDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
Hyungju ParkDivision of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0002-9010-9434
Douglas O KelkhoffDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0009-0003-7845-4061
Cheen Euong AngDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Marius WernigDepartment of Pathology and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-5309-515X
Andrea KaskoDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID 0000-0003-2355-6258
Timothy L DowningDepartment of Biomedical Engineering, University of California, Irvine, Irvine, CA 92617, USA.ORCID 0000-0002-5197-3684
Mu-Ming PooDivision of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0001-5494-6975
Song LiDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID 0000-0002-4760-8828
University of California, Los Angeles · USUniversity of California, Berkeley · USCalifornia Institute for Regenerative Medicine · USUniversity of California, Irvine · USChinese Academy of Sciences · CNKorea Brain Research Institute · KR

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
Regenerative Musculoskeletal Medicine Training ProgramT32AR059033 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI John S Adams, Nicholas M. Bernthal · 2011 to 2026
$4.8M
Spatial epigenomics: A new framework for overcoming mechanical heterogeneity in solid tumorsDP2CA250382 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI DOWNING, TIMOTHY LAMONT · 2019 to 2019
$2.4M
Mechanopriming for cell engineeringR01NS130677 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Song Li · 2023 to 2026
$2.1M
Training Program in Cardiovascular Applied Research and EntrepreneurshipT32HL116270 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W. · 2013 to 2022
$1.6M
Regulation of cell reprogramming by matrix stiffnessR01GM143485 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, SONG · 2021 to 2024
$1.3M
Role of spatial heterogeneous matrix stifness in development of craniofacial tissue interfacesF31DE026356 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NORRIS, SAM CARSTEN-PUISIS · 2017 to 2018
$90k
NCI NIH HHS DP2 CA250382NCI NIH HHS P30 CA016042NHLBI NIH HHS T32 HL116270NIAMS NIH HHS T32 AR059033NIDCR NIH HHS F31 DE026356NIGMS NIH HHS R01 GM143485NINDS NIH HHS R01 NS130677
6 · The paper itself

Abstract

We investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on 20 kPa matrices, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the cotransporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. Our findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.

Indexed as

Cellular ReprogrammingChromatinEpigenesis, GeneticFibroblastsChromatin

Identifiers

PMID38354231
PMCPMC10866547
OpenAlexW4391807416

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.