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Record W4283659847 · doi:10.1101/2022.06.27.497734

KDR Signaling in Muscle Stem Cells Promotes Asymmetric Division and Progenitor Generation for Efficient Regeneration

2022· preprint· en· W4283659847 on OpenAlexafffund
William Chen, Yu Xin Wang, Morten Ritso, Theodore J. Perkins, Michael A. Rudnicki

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsOttawa HospitalUniversity of Ottawa
FundersStem Cell NetworkOttawa Hospital Research InstituteUniversity of Ottawa
KeywordsAsymmetric cell divisionCell biologyBiologyProgenitor cellStem cellRegeneration (biology)Cell divisionDystrophinMyogenesisMyocyteSkeletal muscleCellGeneticsEndocrinology

Abstract

fetched live from OpenAlex

SUMMARY The regulation of muscle stem cell (MuSC) asymmetric division plays an essential role in controlling the growth and repair of skeletal muscle. We discover kinase domain receptor (KDR) as a positive modulator of MuSC asymmetric division using an in-niche high-content screen and confirmed its expression in satellite cells by ddPCR and immunofluorescence. Knockdown of KDR significantly reduces the numbers of asymmetric divisions, whereas ligand stimulation of KDR increases the numbers of asymmetric divisions. KDR signaling is impaired in dystrophin-deficient satellite cells and requires a polarized cell environment established by the dystrophin glycoprotein complex (DGC) to direct asymmetric division. Mice lacking KDR in MuSCs exhibit reduced numbers of satellite cells due to precocious differentiation, and deficits in regeneration consistent with impaired asymmetric division and reduced generation of progenitors. Therefore, our experiments identify KDR signaling as playing an essential role in MuSC function in muscle regeneration. HIGHLIGHTS KDR and VEGFA are expressed in satellite cells Ligand activated KDR stimulates asymmetric satellite stem cell division KDR signaling requires the presence of the DGC KDR-deficient satellite cells give rise to reduced numbers of progenitors eTOC blurb Chen et al., performed a chemical screen using a novel screening platform to identify modulators of muscle stem cell asymmetric division. They discovered that KDR signalling requires the presence of the dystrophin associated glycoprotein complex and is an important regulator of muscle stem cell asymmetric division.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.226
Teacher spread0.211 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicMuscle Physiology and DisordersFrench-language works237,207