Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial differentiation

ABSTRACT: The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Moreover, neurotrophin receptors (NTRs) are significantly upregulated in myoepithelial cells (MECs) post-IR, and scRNAseq revealed that MECs are a main source of neurotrophin ligands. Using two ex vivo models, we show that nerve growth factor (NGF) is essential for MEC differentiation during development, whereas upregulation of NTRs in adult MECs is associated with differentiation defects. The latter morphological abnormalities were confirmed in MECs of human IR glands. As MECs are required for proper acinar cell contraction and secretion, we propose that MEC-specific upregulation of NTRs post-IR disrupts MEC differentiation and potentially hinders the ability of the gland to regenerate.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206878 | GEO | 2023/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lacrimal gland myoepithelial cells are altered in a mouse model of dry eye disease

Project description:The purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sjogren’s syndrome. MECs were cultured from lacrimal glands of C57BL/6J (wild type, WT), and thrombospondin 1 knockout null (TSP1 -/- ) mice. We used microarray to analyzed the differential expression of genes in cultured MECs of TSP1-/- and wild type (WT) mice.

2020-06-25 | GSE150771 | GEO

miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands [mRNA]

Project description:We used mRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.

2022-03-03 | GSE169753 | GEO

miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands [miRNA]

Project description:We used miRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.

2022-03-03 | GSE169692 | GEO

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [female]

Project description:FGF signaling is essential for salivary gland (SG) development and heparan sulfate (HS) regulation of FGFR function is determined by immense structural diversity of sulfated HS domains. The basement membrane (BM), containing HS proteoglycans, collagens and laminins, separates epithelia from stroma and controls growth factor-matrix cross-talk. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS) and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs), which produce BM and are a growth factor signaling hub. To investigate 3-O-HS regulation of MEC function and growth factor signaling, we generated Hs3st3a1;Hs3st3b1 double knockout (DKO) mice. The DKO HS loses specific highly 3-O-sulfated tetrasaccharides, which increases FGF/FGFR-complex binding to HS. During development this leads to increased FGFR-, BM- and MEC-related gene expression. However, in adult DKO SGs the secretory units containing acinar and MECs, have reduced MECs, increased BM and disrupted acinar polarity, resulting in salivary hypofunction. We used defined 3-O-sulfated-HS in FGFR pulldown assays and primary organ cultures to investigate 3-O-HS-dependent mechanisms regulating MEC development. We find that 3-O-HS modulates FGFR signaling to regulate MEC BM synthesis which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.

2024-08-02 | GSE235185 | GEO

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [male]

2024-08-02 | GSE235184 | GEO

Gene expression profiling of mouse CRTC1-MAML2-driven MEC-like tumors

Project description:We established a transgenic CRTC1-MAML2 fusion mouse model and crossed it with the MMTV-Cre transgenic mouse line to induce Cre expression and consequently the CRTC1-MAML2 fusion transgene expression in salivary glands. We observed that Cre-induced CRTC1-MAML2 transgene expression caused the formation of salivary gland tumors resembling the histological features of human MEC. Here we performed genome-wide gene expression profiling analysis to characterize the transcriptomic feature of these murine CRTC1-MAML2-driven MEC-like tumors.

2024-05-10 | GSE143264 | GEO

scRNAseq of healthy and irradiated mouse parotid glands highlights crosstalk between immune and secretory cells during chronic injury

Project description:Translational frameworks to understand the chronic loss of salivary dysfunction that follows after clinical irradiation, and the development of regenerative therapies remain an unmet need. Advances in single cell (sc)RNAseq has made it possible to identify previously uncharacterized cell types within tissues and to uncover gene regulatory networks that mediate cell-cell communication and drive specific cell states. scRNAseq studies have been performed for virtually all major tissues including salivary glands; however, there are currently no scRNAseq studies on chronically irradiated salivary glands. Here, we present scRNAseq from control and irradiated parotid glands from mouse collected 10 months post-irradiation. We identify a previously uncharacterized population of epithelial cells in the gland defined by expression of Etv1, which could be a possible salivary precursor. Furthermore, our data suggests that CD8+ T-cells and secretory cells are the most transcriptionally affected during chronic injury with radiation, suggesting active immune involvement during chronic irradiation injury. Notably, scRNAseq of in vivo models of chronic IR injury has only been performed in liver, lung, and skin, and data is only publicly available for lung and skin. Thus, our study will also be an essential resource to better understand cell-specific responses to chronic irradiation in general.

2023-03-23 | GSE223516 | GEO

Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

Project description:To investigate the timing of endogenous regenerative events in response to a single 10 Gy dose of IR, we sequeced the transcriptomes of glands from adult (6-7 wks)mice and 7- and 14-days post-IR. We then compared to the radiated glands to Non-IR (no radiation) controls, and performed differential expression analysis.

2022-12-28 | GSE209931 | GEO

Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Project description:Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100â250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrophostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition. Reproduction (2009) 138, pp. 697-707 We used microarrays to determine genes expressed differentially between control and NT3 (neurotrophin-3) treated P4 ovary. RNA samples from 3 control groups are compared to 3 NT3 treated ovary groups.

2010-02-21 | E-GEOD-20358 | biostudies-arrayexpress

Expression data from sheroids cultured in medium that promotes myoepithelial or proacinar differentiation

Project description:We identifiied culture conditions that promoted the differentiation of the murine salivary gland epithelial cell line, mSG-PAC1 towards myoepithelial or proacinar cell fates, which were characterized by the expression of known cell type markers. Differentiation gene expression was analyzed and GSEA was performed comparing the resulting transcirptomes and published sc_RNA seq data for murine salivary gland myoepithleial and acinar cells

2022-03-02 | GSE197652 | GEO

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