Integratingin silicopredictions with an engineered tissue assay identifies Perlecan as an age-perturbed re-quiescence cue for muscle stem cells DOI Open Access

Erik Jacques,

Pauline Garcia,

Orane Mercier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

Abstract Skeletal muscle regeneration is mediated by resident stem cells that produce progeny to repair or recreate muscle. Critical this function the ability transition between states of proliferation and quiescence. This balancing act disrupted with age, leading eroded regenerative capacity. Notwistanding, mechanisms which regenerating niche directs MuSCs return dormant state are largely unknown. Since single-cell RNAseq methods exclude analysis multinucleated cells, we generated single-nuclei datasets capture full breadth myogenic progression. With this, uncovered new differentiating myocytes syncytial cells. Using cell communication inference tools, highlighted receptor-ligand interactions fusing nuclei. We leveraged a bespoke biomimetic 3D induces MuSC quiescence, filter predicted using Cas9-based functional genomics approach. found proteoglycan Perlecan (Hspg2) promotes re-quiescence. Hspg2 silencing in vivo , during regeneration, induced an aging-like phenotype perturbed Notably, temporal profile overall levels were altered age. Exogenous supplementation Endorepellin (truncated Perlecan) rescued decline following aged offering therapeutic target. Thus, coupling silico predictions vitro assay followed investigations revealed previously inaccessible window biology; spatiotemporal coordination re-quiescence directed myonuclei.

Language: Английский

Functional specialisation and coordination of myonuclei DOI
Amaury Korb, Shahragim Tajbakhsh, Glenda Comai

et al.

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2024, Volume and Issue: 99(4), P. 1164 - 1195

Published: March 13, 2024

ABSTRACT Myofibres serve as the functional unit for locomotion, with sarcomere fundamental subunit. Running entire length of this structure are hundreds myonuclei, located at periphery myofibre, juxtaposed to plasma membrane. Myonuclear specialisation and clustering centre ends fibre known be essential muscle contraction, yet molecular basis regionalisation has remained unclear. While ‘myonuclear domain hypothesis’ helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on diverse transcriptional programs running simultaneously within syncytia added a new perspective communicate. Building upon this, we explore critical cellular sources heterogeneity myofibres, discussing impact intrinsic extrinsic factors myonuclear programs. This knowledge provides insights understanding development, repair, disease, but also opens avenues development precise therapeutic approaches.

Language: Английский

Citations

3
Measurement of Myonuclear Accretion In Vitro and In Vivo DOI
Lola Lessard,

Audrey Saugues,

Julien Gondin

et al.

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Integratingin silicopredictions with an engineered tissue assay identifies Perlecan as an age-perturbed re-quiescence cue for muscle stem cells DOI Open Access

Erik Jacques,

Pauline Garcia,

Orane Mercier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

Abstract Skeletal muscle regeneration is mediated by resident stem cells that produce progeny to repair or recreate muscle. Critical this function the ability transition between states of proliferation and quiescence. This balancing act disrupted with age, leading eroded regenerative capacity. Notwistanding, mechanisms which regenerating niche directs MuSCs return dormant state are largely unknown. Since single-cell RNAseq methods exclude analysis multinucleated cells, we generated single-nuclei datasets capture full breadth myogenic progression. With this, uncovered new differentiating myocytes syncytial cells. Using cell communication inference tools, highlighted receptor-ligand interactions fusing nuclei. We leveraged a bespoke biomimetic 3D induces MuSC quiescence, filter predicted using Cas9-based functional genomics approach. found proteoglycan Perlecan (Hspg2) promotes re-quiescence. Hspg2 silencing in vivo , during regeneration, induced an aging-like phenotype perturbed Notably, temporal profile overall levels were altered age. Exogenous supplementation Endorepellin (truncated Perlecan) rescued decline following aged offering therapeutic target. Thus, coupling silico predictions vitro assay followed investigations revealed previously inaccessible window biology; spatiotemporal coordination re-quiescence directed myonuclei.

Language: Английский

Citations

0