Evidence map›Paper›PMID 35421801›Full record

ArticleBiomaterials2022

Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells.

Jason Wang, Torie Broer, Taylor Chavez, Chris J Zhou, Sabrina Tran, Yu Xiang, Alastair Khodabukus, Yarui Diao, Nenad Bursac

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2022. 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, 23 citations in OpenAlex.

  1. Article
  2. RYR1Journal of translational medicine · 2026
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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

9 authors at 1 institution in 1 country.

Jason WangDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Torie BroerDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Taylor ChavezDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Chris J ZhouDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Sabrina TranDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Yu XiangDepartment of Cell Biology, Duke University, Durham, NC, USA.
Alastair KhodabukusDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Yarui DiaoDepartment of Cell Biology, Duke University, Durham, NC, USA.
Nenad BursacDepartment of Biomedical Engineering, Duke University, Durham, NC, USA. Electronic address: nbursac@duke.edu.
Duke University · US

Funding

Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS-CoV-2 Drug ScreeningUH3TR002142 · NCATS · DUKE UNIVERSITY · PI TRUSKEY, GEORGE A · 2019 to 2021
$4.0M
Stable therapy in Pompe disease through genome editingR01AR079223 · NIAMS · DUKE UNIVERSITY · PI KOEBERL, DWIGHT D · 2021 to 2025
$3.3M
University Training Program in Biomolecular and Tissue EngineeringT32GM144291 · NIGMS · DUKE UNIVERSITY · PI Charles A. Gersbach, Tatiana Segura · 2022 to 2026
$2.6M
Microphysiological Human Tissue Systems for Monitoring of Genome Editing OutcomesU01HL156348 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD, GERSBACH, CHARLES A. · 2020 to 2022
$2.0M
Muscle-macrophage constructs for skeletal muscle repairR01AR070543 · NIAMS · DUKE UNIVERSITY · PI BURSAC, NENAD · 2016 to 2020
$1.9M
Translational studies of GAA deficiency in bioengineered human muscleR01AR065873 · NIAMS · DUKE UNIVERSITY · PI BURSAC, NENAD, KOEBERL, DWIGHT D · 2013 to 2017
$1.8M
Microphysiological Human Tissue Systems for Monitoring of Genome Editing OutcomesU01EB028901 · NIBIB · DUKE UNIVERSITY · PI BURSAC, NENAD, GERSBACH, CHARLES A. · 2019 to 2019
$668k
Genome editing for the correction of Pompe diseaseR21AR073470 · NIAMS · DUKE UNIVERSITY · PI KOEBERL, DWIGHT D · 2020 to 2021
$373k
NCATS NIH HHS UH3 TR002142NHLBI NIH HHS U01 HL156348NIAMS NIH HHS R01 AR065873NIAMS NIH HHS R01 AR070543NIAMS NIH HHS R01 AR079223NIAMS NIH HHS R21 AR073470NIBIB NIH HHS U01 EB028901NIGMS NIH HHS T32 GM144291
6 · The paper itself

Abstract

Satellite cells (SCs), the adult Pax7-expressing stem cells of skeletal muscle, are essential for muscle repair. However, in vitro investigations of SC function are challenging due to isolation-induced SC activation, loss of native quiescent state, and differentiation to myoblasts. In the present study, we optimized methods to deactivate in vitro expanded human myoblasts within a 3D culture environment of engineered human skeletal muscle tissues ("myobundles"). Immunostaining and gene expression analyses revealed that a fraction of myoblasts within myobundles adopted a quiescent phenotype (3D-SCs) characterized by increased Pax7 expression, cell cycle exit, and activation of Notch signaling. Similar to native SCs, 3D-SC quiescence is regulated by Notch and Wnt signaling while loss of quiescence and reactivation of 3D-SCs can be induced by growth factors including bFGF. Myobundle injury with a bee toxin, melittin, induces robust myofiber fragmentation, functional decline, and 3D-SC proliferation. By applying single cell RNA-sequencing (scRNA-seq), we discover the existence of two 3D-SC subpopulations (quiescent and activated), identify deactivation-associated gene signature using trajectory inference between 2D myoblasts and 3D-SCs, and characterize the transcriptomic changes within reactivated 3D-SCs in response to melittin-induced injury. These results demonstrate the ability of an in vitro engineered 3D human skeletal muscle environment to support the formation of a quiescent and heterogeneous SC population recapitulating several aspects of the native SC phenotype, and provide a platform for future studies of human muscle regeneration and disease-associated SC dysfunction.

Indexed as

Satellite Cells, Skeletal MuscleAnimalsCell DifferentiationCell ProliferationHumansMelittenMuscle, SkeletalMelittenActivationEngineered skeletal muscleHumanQuiescenceSatellite cellsscRNA-seq

Identifiers

PMID35421801
PMCPMC9289780
OpenAlexW4223994474

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.