Evidence map›Paper›PMID 30120125›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Material microenvironmental properties couple to induce distinct transcriptional programs in mammalian stem cells.

Max Darnell, Alison O'Neil, Angelo Mao, Luo Gu, Lee L Rubin, David J Mooney

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
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  5. Review
  6. Review
  7. Article
  8. Review
  9. Biomaterials for Cell Manufacturing.ACS macro letters · 2024
    Article
  10. Matrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Substrate stress relaxation regulates neural stem cell fate commitment.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Cell-extracellular matrix mechanotransduction in 3D.Nature reviews. Molecular cell biology · 2023
    Review
  18. Article
  19. The Application of Porous Scaffolds for Cardiovascular Tissues.Bioengineering (Basel, Switzerland) · 2023
    Review
  20. Article
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

6 authors at 1 institution in 1 country.

Max DarnellJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Alison O'NeilDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
Angelo MaoJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Luo GuJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Lee L RubinDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
David J MooneyJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; mooneyd@seas.harvard.edu.
Harvard University · US

Funding

POLYMERIC MATRICES WITH DEFINED CELL ADHESION AND MECHANR01DE013033 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOONEY, DAVID J · 1998 to 2018
$3.0M
NIDCR NIH HHS R01 DE013033
6 · The paper itself

Abstract

Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other features; meanwhile, mechanistic studies have detailed a number of biophysical mechanisms for this sensing. However, the broad molecular consequences of these potentially complex and nonlinear interactions bridging from biophysical sensing to phenotype have not been systematically characterized, limiting the overall understanding and rational deployment of these biophysical cues. Here, we explore these interactions by employing a 3D cell culture system that allows for the independent control of culture substrate stiffness, stress relaxation, and adhesion ligand density to systematically explore the transcriptional programs affected by distinct combinations of biophysical parameters using RNA-seq. In mouse mesenchymal stem cells and human cortical neuron progenitors, we find dramatic coupling among these substrate properties, and that the relative contribution of each property to changes in gene expression varies with cell type. Motivated by the bioinformatic analysis, the stiffness of hydrogels encapsulating mouse mesenchymal stem cells was found to regulate the secretion of a wide range of cytokines, and to accordingly influence hematopoietic stem cell differentiation in a Transwell coculture model. These results give insights into how biophysical features are integrated by cells across distinct tissues and offer strategies to synthetic biologists and bioengineers for designing responses to a cell's biophysical environment.

Indexed as

AlginatesHydrogelsStem Cell NicheAnimalsCell Culture TechniquesCell DifferentiationGlucuronic AcidHematopoietic Stem CellsHexuronic AcidsMesenchymal Stem CellsMiceTranscription, GeneticAlginatesGlucuronic AcidHexuronic AcidsHydrogelsbiomaterialsmechanotransductionRNA-seqstem cellssystems biology

Identifiers

PMID30120125
PMCPMC6130338
OpenAlexW2887937567

What OpenQuestion holds

Textmetadata
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.