Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DELTA1/NOTCH2-mediated signaling regulates muscle stem cell self-renewal

ABSTRACT: How satellite cells and their progenitors balance differentiation and self-renewal to achieve sustainable tissue regeneration is not well understood. A major roadblock to understanding satellite cell fate decisions has been the difficulty to study this process in vivo. By visualizing expression dynamics of myogenic transcription factors during early regeneration in vivo, we identified the time point at which cells undergo decisions to differentiate or self-renew. Single-cell RNA sequencing revealed heterogeneity of satellite cells during both muscle homeostasis and regeneration, including a subpopulation enriched in Notch2 receptor expression. Furthermore, we reveal that differentiating cells express the Dll1 ligand. Using antagonistic antibodies we demonstrate that the DLL1 and NOTCH2 signaling pair is required for satellite cell self-renewal. Thus, differentiating cells provide the self-renewing signal during regeneration, enabling proportional regeneration in response to injury while maintaining the satellite cell pool. These findings have implications for therapeutic control of muscle regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE142581 | GEO | 2019/12/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state

Project description:Successful skeletal muscle regeneration is primarily mediated by muscle stem cells or satellite cells which express Pax7. In homeostasis, these satellite cells exist in a ‘genuine quiescent’ state, although some satellite cells may also be primed. After an acute injury, satellite cells, enabled by several other niche cells in the muscle tissue, undergo a series of molecular and cellular changes such as activation, proliferation, and differentiation. These processes culminate in the generation of nascent muscle fibers or the restoration of worn-out muscle fibers, leading to the restoration of muscle function. To prevent the depletion of the quiescent satellite cell pool, some satellite cells must resist the ambient differentiation signals and undergo the self-renewal process. While the differentiation process has been well characterized, little is known about the mechanism of satellite cell self-renewal. Furthermore, the molecular identity of self-renewing satellite cells remains unknown. To fill this gap, we utilize single nuclei ATACseq with high temporal resolution to characterize the temporal dynamics of chromatin accessibility in satellite cells and other muscle niche cells during muscle regeneration. This enables us to identify for the first time the self-renewing trajectory undertaken by satellite cells for their long-term repopulation. We also validated these findings using single-cell RNAseq and other protein-level assays. We also utilize gene perturbation to show that SMAD4, a co-SMAD regulating the TGF-beta pathway regulates the cfate choice of self-renewal versus differentiation.

2023-06-18 | GSE199499 | GEO

P38 signaling underlies a cell-autonomous loss of stem cell self-renewal in aged muscle

Project description:Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via novel alterations in FGF and p38αβ MAPK signaling in old satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveals potential therapeutic opportunities for the treatment of progressive muscle wasting. Satellite cells were isolated from young (3-6mo) and aged (20-25mo) adult mice; individual date files represent 2 independent pools of RNA from 4-8 mice at each timepoint.

2013-09-01 | E-GEOD-47104 | biostudies-arrayexpress

Notch2 Expressed by Myofibers Influences Muscle Mass and Fiber Types

Project description:Notch receptors play crucial roles in the cell-fate decisions of tissue stem cells during development and regeneration. Notch1-3 receptors are expressed by satellite cells and their progeny. Here we found that Notch2, but not Notch1 or Notch3, was expressed in fully differentiated myofibers. Using transgenic mice that expressed a muscle-specific active form of Notch2 (N2ICD-mTG), we found that Notch2 activation remarkably reduced muscle mass and strength with a shift toward slow fibers. Transcriptome analyses revealed that growth differentiation factor 11 (GDF11) was highly up-regulated in muscles of N2ICD-mTG mice, and crucially, N2ICD-induced muscle atrophy was rescued by siRNA-mediated reduction of GDF11 expression. These data suggest that Notch2 functions in muscle to regulate muscle mass, in part, through induction of GDF11 expression, and reveal a novel aspect of Notch signaling in a terminally differentiated adult tissue.

2020-01-01 | GSE83929 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 3; Adult vs. Young)

2013-12-31 | GSE53726 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 1; Geriatric vs. Young)

2013-12-31 | GSE53724 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 2; Old/Geriatric vs. Young and SAMR1 vs. SAMP8)

2013-12-31 | GSE53725 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence

2013-12-31 | GSE53728 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 3; Adult vs. Young)

Project description:Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with aging. We report that geriatric satellite cells, compared to old and adult cells, are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and this irreversibly affects their intrinsic regenerative and self-renewal capacities. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging. Pure satellite cell populations from dissociated skeletal muscle from Young (2-3 months) and Adult (6 months) mice were isolated using a well-established flow cytometry protocol gating on integrin a7(+)/CD34(+) (positive selection) and Lin- (CD31, CD45, CD11b, Sca1) (negative selection).

2013-12-31 | E-GEOD-53726 | biostudies-arrayexpress

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 1; Geriatric vs. Young)

Project description:Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with aging. Here we report that geriatric satellite cells, compared to old cells, are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and this irreversibly affects their intrinsic regenerative and self-renewal capacities. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging. Pure satellite cell populations from dissociated skeletal muscle from Young (2-3 months) and Geriatric (28-32 months) mice were isolated using a well-established flow cytometry protocol gating on integrin a7(+)/CD34(+) (positive selection) and Lin- (CD31, CD45, CD11b, Sca1) (negative selection).

2013-12-31 | E-GEOD-53724 | biostudies-arrayexpress

Expression data from skeletal muscle satellite cells at different development stages

Project description:Satellite cells are responsible for the long-term regenerative capacity of adult skeletal muscle. The diminished muscle performance and regenerative capacity of aged muscle is thought to reflect progressive fibrosis and atrophy. Whether this reduction in muscle competency also involves a diminishment in the intrinsic regulation of satellite cell self-renewal remains unknown. We used microarray to identify gene expression changes underlying the marked reduction in the capacity of satellite cells to self-renew, contribute to regeneration and repopulate the niche as they age. Skeletal muscles from heterozygous Pax7-ZsGreen mice were isolated at defined stages: E17.5 (fetal - whole forelimb and hindlimb), postnatal day 21 (adolescent - hindlimb), 2-3 month old (young adult - hindlimb) and >1 year old (older adult - hindlimb) mice. ZsGreen-positive skeletal muscle satellite cells were isolated by FACS and pooled (fetal n=4, adolescent n=6, young adult n=8 and older adult n=8 mice).

2014-05-26 | E-GEOD-47401 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data