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Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [RNA-seq]

ABSTRACT: The goal of this study is to compare transcriptome profiling (RNA-seq) of proximal end of incisor 1 week after TMX induction between control and Fgfr1 mutant mice

ORGANISM(S): Mus musculus

PROVIDER: GSE197785 | GEO | 2023/01/31

REPOSITORIES: GEO

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Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis.

Project description:Mesenchymal stem cells (MSCs) reside in microenvironments, referred to as niches, which provide structural support and molecular signals. Sensory nerves are niche components in the homeostasis of tissues such as skin, bone marrow and hematopoietic system. However, how the sensory nerve affects the behavior of MSCs remains largely unknown. Here we show that the sensory nerve is vital for mesenchymal tissue homeostasis and maintenance of MSCs in the continuously growing adult mouse incisor. Loss of sensory innervation leads to mesenchymal disorder and a decrease in MSCs. Mechanistically, FGF1 from the sensory nerve directly acts on MSCs by binding to FGFR1 and activates the mTOR/autophagy axis to sustain MSCs. Modulation of mTOR/autophagy restores the MSCs and rescues the mesenchymal tissue disorder of Fgfr1 mutant mice. Collectively, our study provides insights into the role of sensory nerves in the regulation of MSC homeostasis and the mechanism governing it.

| S-EPMC9859800 | biostudies-literature

Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-26 | GSE197787 | GEO

Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [scRNA-seq]

Project description:In this study, using the mouse molar as a model, we took advantage of single-cell transcriptome profiling, lineage tracing and transgenic mouse models to interrogate the cellular heterogeneity and gene regulatory networks (GRNs) of postmigratory CNCCs.In this study, we have put together a dynamic spatiotemporal single-cell regulatory atlas and revealed the landscape of transcriptional heterogeneity and defined the cellular domains during the progression of cranial neural crest cell (CNCC)-derived dental lineage diversification. Importantly, we identified cell type-specific gene regulatory networks (GRNs) during CNCC-derived dental lineage development.

2022-10-26 | GSE197786 | GEO

Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis.

Project description:Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis.

| PRJNA812031 | ENA

Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [scRNA-seq]

Project description:Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [scRNA-seq]

| PRJNA812042 | ENA

Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [RNA-seq]

Project description:Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis [RNA-seq]

| PRJNA812043 | ENA

FGF signaling modulates mechanical force/WNT signaling in progenitors during tooth root development

Project description:The goal of this study is to compare transcriptome profiling (RNA-seq) of apical part of molar at postnatal 7.5 days after TMX induction between control and Fgfr1 mutant mice

2024-02-28 | GSE233576 | GEO

Sensory nerve regulates progenitor cells via FGF-ETV5/PTCH1-Hh axis during tooth root morphogenesis

Project description:The goal of this study is to investigate the role of nerve in tooth root morphogenesis

2023-12-21 | GSE224471 | GEO

Gene expression profiling of murine incisor pulp following resection of the inferior alveolar nerve

Project description:The overall goal of this project is to investigate the contribution of the inferior alveolar nerve (IAN) towards cellular mechanisms required for regeneration of the murine incisor. Here, we conducted gene expression profiling of adult murine incisor dental mesenchyme tissue following two weeks after unilateral resection of the IAN from both the denerved and contralateral incisor of five wild-type mice.

2014-12-30 | GSE51479 | GEO

Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors.

Project description:There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer clinical trials, was tested in two human MPNST xenograft models (STS26T and MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765 abrogated human MPNST local and metastatic growth in severe combined immunodeficient mice. Notably, this therapeutic approach failed to induce apoptosis in MPNST cells but rather resulted in marked productive autophagy. Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic regimen of MPNST xenografts after pretreatment with XL765 resulted in superior antitumor effects as compared with either agent alone. Together, preclinical studies described here expand our previous findings and suggest that PI3K/mTOR inhibition alone and (most importantly) in combination with autophagy blockade may comprise a novel and efficacious therapy for patients harboring MPNST.

| S-EPMC3416967 | biostudies-literature

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