DELTA1/NOTCH2-mediated signaling regulates muscle stem cell self-renewal
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597534 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2019-12-25 | GSE142581 | GEO
Project description:In this study we demonstrate that Tgif1 has a role in HSCs maintenance, self-renewal and quiescence. RNA sequencing data of LSK cells (HSCs enriched cell population) from Tgif1-/- and wild type mice implicates that multiple pathways involved in HSC quiescence and self-renewal are disturbed in Tgif1 deficient mice. RNA expression profiles of wild type (WT) and Tgif1-/- LSK cells were generated by RNA sequencing, in triplicate, using Illumina HiSeq 2000.
2013-09-10 | E-GEOD-50739 | biostudies-arrayexpress
Project description:In this study we demonstrate that Tgif1 has a role in HSCs maintenance, self-renewal and quiescence. RNA sequencing data of LSK cells (HSCs enriched cell population) from Tgif1-/- and wild type mice implicates that multiple pathways involved in HSC quiescence and self-renewal are disturbed in Tgif1 deficient mice.
2013-09-10 | GSE50739 | GEO
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use single cell RNAseq to identify the innate metabolic signature of muscle stem cells. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment, suggesting local metabolite production may be a therapeutic target to improve muscle regeneration.
2018-07-18 | GSE117229 | GEO
Project description:Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use single cell RNAseq to identify the innate metabolic signature of muscle stem cells. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment, suggesting local metabolite production may be a therapeutic target to improve muscle regeneration.
2021-07-18 | GSE117386 | GEO
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
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation. Three biological replicates of asymmetrically self-renewing cultures (Asym1-3) were compared with cultures that were symmetrically self-renewing - either because they did not express p53 (3 biological replicates, Sym1-3) or they expressed constitutive IMPDH II (i.e., not regulated by p53) as well as p53 (2 biological replicates, Symp53_1 and 2.)
2010-12-22 | E-GEOD-25334 | biostudies-arrayexpress
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation.
2010-12-22 | GSE25334 | GEO
Project description:Embryonic stem cells (ESCs) can self-renew indefinitely and have the potential to differentiate into all cell types in the adult organism. Although the developmental plasticity of ESCs is mainly controlled by transcription factors, the intrinsic regulation of this process remains elusive. Here, using whole transcriptome RNA-sequencing analysis, we identified branched-chain amino acid aminotransferase-1 (Bcat1) as highly expressed in mouse ESCs. Further, deletion of the Bcat1 gene was found to impair the pluripotency and self-renewal of mouse ESCs and made cells more inclined to differentiate toward epiblast stem cells. Conversely, overexpression of Bcat1 in mouse ESCs resulted in robust self-renewal and the repression of differentiation. Mechanistically, Bcat1 regulates the expression of RAS protein activator like 1 (Rasal1), leading to activation of Ras-Erk/MAPK signaling axis, which controls the expression of a set of core transcription factors that maintain pluripotency and self-renewal. In summary, we identified for the first time that Bcat1 is essential for mouse ESCs self-renewal and pluripotency and that this effect is mediated by the Ras pathway.
2019-01-16 | GSE125023 | GEO