Evidence map›Paper›PMID 33122122›Full record

ArticleMolecular metabolism2021

Extracellular serine and glycine are required for mouse and human skeletal muscle stem and progenitor cell function.

Brandon J Gheller, Jamie E Blum, Esther W Lim, Michal K Handzlik, Ern Hwei Hannah Fong, Anthony C Ko, Shray Khanna, Molly E Gheller, Erica L Bender, Matthew S Alexander and 5 more

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

Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

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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

15 authors at 4 institutions in 1 country.

Brandon J GhellerDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Jamie E BlumDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Esther W LimDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Michal K HandzlikDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Ern Hwei Hannah FongMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Anthony C KoDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Shray KhannaDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Molly E GhellerDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Erica L BenderDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Matthew S AlexanderDepartment of Pediatrics, Division of Neurology at the University of Alabama at Birmingham and Children's of Alabama, Birmingham, AL, USA; UAB Center for Exercise Medicine, Birmingham, AL, USA; Civitan International Research Center at the University of Alabama at Birmingham, Birmingham, AL, USA; Department of Genetics at the University of Alabama at Birmingham, Birmingham, AL, USA.
Patrick J StoverCollege of Agriculture and Life Sciences, Texas A&M University, College Station, TX, USA.
Martha S FieldDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Benjamin D CosgroveMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Christian M MetalloDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Anna E Thalacker-MercerDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA; UAB Center for Exercise Medicine, Birmingham, AL, USA; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, USA. Electronic address: athalack@uab.edu.
Cornell University · USUniversity of California San Diego · USCivitan International · USTexas A&M University · US

Funding

Training in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8M
Revealing muscle stem cell heterogeneity in mice and humans through deep single-cell analysisR01AG058630 · NIA · CORNELL UNIVERSITY · PI COSGROVE, BENJAMIN DAVID · 2018 to 2022
$2.9M
Non-essential amino acids and sphingolipid diversity in cancer progressionR01CA234245 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI METALLO, CHRISTIAN MICHAEL · 2019 to 2023
$1.9M
A MIR-486/DOCK3 SIGNALING AXIS MODULATES DYSTROPHIN-DEFICIENT PATHOLOGYR01HD095897 · NICHD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ALEXANDER, MATTHEW SCOTT · 2018 to 2022
$1.6M
Modeling and analysis of the mechanochemical processes that govern clathrin-mediated endocytosisR01GM132106 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RANGAMANI, PADMINI · 2020 to 2024
$1.5M
Combinatorial biomimetic systems to enable high-throughput evaluation and expansion of genome-edited dystrophic muscle stem cellsR21AR072265 · NIAMS · CORNELL UNIVERSITY · PI COSGROVE, BENJAMIN DAVID · 2018 to 2019
$397k
Micro RNAs as biomarkers and therapeutic targets in myotubular myopathyR21AR074006 · NIAMS · HOSPITAL FOR SICK CHLDRN (TORONTO) · PI ALEXANDER, MATTHEW SCOTT, DOWLING, JAMES J · 2018 to 2019
$337k
NCI NIH HHS R01 CA234245NIAMS NIH HHS R21 AR072265NIAMS NIH HHS R21 AR074006NIA NIH HHS R01 AG058630NIBIB NIH HHS T32 EB009380NICHD NIH HHS R01 HD095897NIGMS NIH HHS R01 GM132106
6 · The paper itself

Abstract

objectiveSkeletal muscle regeneration relies on muscle-specific adult stem cells (MuSCs), MuSC progeny, muscle progenitor cells (MPCs), and a coordinated myogenic program that is influenced by the extracellular environment. Following injury, MPCs undergo a transient and rapid period of population expansion, which is necessary to repair damaged myofibers and restore muscle homeostasis. Certain pathologies (e.g., metabolic diseases and muscle dystrophies) and advanced age are associated with dysregulated muscle regeneration. The availability of serine and glycine, two nutritionally non-essential amino acids, is altered in humans with these pathologies, and these amino acids have been shown to influence the proliferative state of non-muscle cells. Our objective was to determine the role of serine/glycine in MuSC/MPC function.

methodsPrimary human MPCs (hMPCs) were used for in vitro experiments, and young (4-6 mo) and old (>20 mo) mice were used for in vivo experiments. Serine/glycine availability was manipulated using specially formulated media in vitro or dietary restriction in vivo followed by downstream metabolic and cell proliferation analyses.

resultsWe identified that serine/glycine are essential for hMPC proliferation. Dietary restriction of serine/glycine in a mouse model of skeletal muscle regeneration lowered the abundance of MuSCs 3 days post-injury. Stable isotope-tracing studies showed that hMPCs rely on extracellular serine/glycine for population expansion because they exhibit a limited capacity for de novo serine/glycine biosynthesis. Restriction of serine/glycine to hMPCs resulted in cell cycle arrest in G0/G1. Extracellular serine/glycine was necessary to support glutathione and global protein synthesis in hMPCs. Using an aged mouse model, we found that reduced serine/glycine availability augmented intermyocellular adipocytes 28 days post-injury.

conclusionsThese studies demonstrated that despite an absolute serine/glycine requirement for MuSC/MPC proliferation, de novo synthesis was inadequate to support these demands, making extracellular serine and glycine conditionally essential for efficient skeletal muscle regeneration.

Indexed as

AdultAgedAnimalsCell DifferentiationCell ProliferationCells, CulturedFemaleGlycineHumansMaleMiceMice, Inbred C57BLMuscle DevelopmentMuscle, SkeletalMyoblastsPrimary Cell CultureGlycineSerineGlycine metabolismMuscleMuscle metabolismMuscle progenitor cellMuscle regenerationMuscle stem cellProliferationProtein synthesisSerine metabolism

Identifiers

PMID33122122
PMCPMC7691553
OpenAlexW3094306108

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.