Evidence map›Paper›PMID 34191625›Full record

ArticleAmerican journal of physiology. Cell physiology2021

Skeletal muscle progenitors are sensitive to collagen architectural features of fibril size and cross linking.

Lin-Ya Hu, Cassidy J Mileti, Taryn Loomis, Sarah E Brashear, Sarah Ahmad, Rosemary R Chellakudam, Ross P Wohlgemuth, Marissa A Gionet-Gonzales, J Kent Leach, Lucas R Smith

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  3. A novel protocol for the direct isolation of a highly pure and regenerative population of satellite stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  12. Thrown for a loop: fibro-adipogenic progenitors in skeletal muscle fibrosis.American journal of physiology. Cell physiology · 2023
    Review
  13. Article
  14. Review
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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

10 authors at 1 institution in 1 country.

Lin-Ya HuDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.
Cassidy J MiletiBiomedical Engineering Graduate Group, University of California, Davis, California.
Taryn LoomisBiomedical Engineering Graduate Group, University of California, Davis, California.
Sarah E BrashearDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.
Sarah AhmadDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.
Rosemary R ChellakudamDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.
Ross P WohlgemuthDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.
Marissa A Gionet-GonzalesBiomedical Engineering Graduate Group, University of California, Davis, California.
J Kent LeachDepartment of Biomedical Engineering, University of California, Davis, California.
Lucas R SmithDepartment of Neurobiology, Physiology, and Behavior, University of California, Davis, California.ORCID 0000-0002-7610-4231
University of California, Davis · US

Funding

Dual peptide presentation from bioengineered carriers to potentiate stromal cell function and tissue repairR01DE025899 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2017 to 2021
$2.5M
Biomaterial regulation of cell spheroids to synergistically enhance bone healingR01DE025475 · NIDCR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEACH, J. KENT · 2015 to 2019
$1.9M
The role of collagen organization in determination of fibrotic muscle function and regenerationR00AR067867 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SMITH, LUCAS R · 2018 to 2020
$741k
HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR) R01DE025475HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR) R01DE025899NIAMS NIH HHS R00 AR067867NIDCR NIH HHS R01 DE025475NIDCR NIH HHS R01 DE025899
6 · The paper itself

Abstract

Muscle stem cells (MuSCs) are essential for the robust regenerative capacity of skeletal muscle. However, in fibrotic environments marked by abundant collagen and altered collagen organization, the regenerative capability of MuSCs is diminished. MuSCs are sensitive to their extracellular matrix environment but their response to collagen architecture is largely unknown. The present study aimed to systematically test the effect of underlying collagen structures on MuSC functions. Collagen hydrogels were engineered with varied architectures: collagen concentration, cross linking, fibril size, and fibril alignment, and the changes were validated with second harmonic generation imaging and rheology. Proliferation and differentiation responses of primary mouse MuSCs and immortal myoblasts (C2C12s) were assessed using EdU assays and immunolabeling skeletal muscle myosin expression, respectively. Changing collagen concentration and the corresponding hydrogel stiffness did not have a significant influence on MuSC proliferation or differentiation. However, MuSC differentiation on atelocollagen gels, which do not form mature pyridinoline cross links, was increased compared with the cross-linked control. In addition, MuSCs and C2C12 myoblasts showed greater differentiation on gels with smaller collagen fibrils. Proliferation rates of C2C12 myoblasts were also higher on gels with smaller collagen fibrils, whereas MuSCs did not show a significant difference. Surprisingly, collagen alignment did not have significant effects on muscle progenitor function. This study demonstrates that MuSCs are capable of sensing their underlying extracellular matrix (ECM) structures and enhancing differentiation on substrates with less collagen cross linking or smaller collagen fibrils. Thus, in fibrotic muscle, targeting cross linking and fibril size rather than collagen expression may more effectively support MuSC-based regeneration.

Indexed as

AnimalsCell DifferentiationExtracellular MatrixMiceMuscle DevelopmentMuscle Fibers, SkeletalMuscle, SkeletalMuscular DiseasesMyoblastsMyocytes, CardiacRegenerationcollagen architectureextracellular matrixmuscle differentiationsatellite cellstem cell

Identifiers

PMID34191625
PMCPMC8424678
OpenAlexW3174973204

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.