Biology subjects

Schulz, C.

Publications and source records attributed to Schulz, C..

3 recordsLinked to original sources

bioRxiv2018

G-Protein signaling increases germline stem cell activity in Drosophila males in response to multiple rounds of mating

Adult stem cells divide to renew the stem cell pool and replenish specialized cells that are lost due to death or usage. However, little is known about the mechanisms regulating how stem cells adjust to a demand for specialized cells. A failure of the stem cells to respond to this demand can have serious consequences, such as tissue loss, or prolonged recovery post injury. Here, we challenge the male germline stem cells (GSCs) of Drosophila melanogaster for the production of specialized cells using mating experiments. We show that repeated mating reduced the sperm pool and accelerated germline stem cell (GSC) divisions. The increase in GSC divisions depended on the activity of the highly conserved G-proteins. Germline expression of RNA-Interference (RNA-i) constructs against G-proteins or a dominant negative G-protein eliminated the increase in GSC divisions in mated males. Consistent with a role for the G-proteins in the regulation of GSC divisions, RNA-i against seven out of 35 G-protein coupled receptors (GPCRs) within the germline cells also eliminated the capability of males to accelerate their GSC divisions in response to mating. Our data show that GSCs are receptive to GPCR stimulus, potentially through a network of interactions among multiple signaling pathways.

developmental biology↗

bioRxiv2018

Alzheimer’s disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

The role of microRNAs (miRNAs) in the pathogenesis of Alzheimers disease (AD) is currently extensively investigated. In this study, we assessed the potential impact of AD genetic risk variants on miRNA expression by performing large-scale bioinformatic data integration. Our analysis was based on genetic variants from three AD genome-wide association studies (GWAS). Association with miRNA expression was tested by expression quantitative trait loci (eQTL) analysis using next-generation miRNA sequencing data generated in lymphoblastoid cell lines (LCL). While, overall, we did not identify a strong effect of AD GWAS variants on miRNA expression in this cell type we highlight two notable outliers, i.e. miR-29c-5p and miR-6840-5p. MiR-29c-5p was recently reported to be involved in the regulation of BACE1 and SORL1 expression. In conclusion, despite two exceptions our large-scale assessment provides only limited support for the hypothesis that AD GWAS variants act as miRNA eQTLs.

genetics↗

bioRxiv2018

TGF-βRII knock-down promotes tumor growth and chemoresistance to gemcitabine of pancreatic cancer cells via phosphorylation of STAT3

Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers in the western countries because of a lack of early diagnostic markers and efficient therapeutics. At the time of diagnosis, more than 80% of patients have metastasis or locally advanced cancer and are therefore not eligible for surgical resection. Pancreatic cancer cell also harbour a high resistance to chemotherapeutic drugs such as gemcitabine that is one of the main palliative treatment for PDAC.\n\nTGF-{beta} possesses both tumor-suppressive and oncogenic activities in pancreatic cancer. TGF-{beta} signalling pathway plays complex role during carcinogenesis by initially inhibiting epithelial growth and later promoting the progression of advanced tumors and thus emerged as tumor suppressor pathway. TGF-{beta} binds to its receptor TGF-{beta}RII and activates different pathways: canonical pathway involving the Smad proteins and alternative pathways such as MAPKs. Smad4 is mutated in 50-80% of PDAC. Mutations of TGF-{beta}RII also occurs (5-10%). In order to decipher the role of TGF-{beta} in carcinogenesis and chemoresistance, we decided to characterize the knocking down of TGF-{beta}RII that is the first actor of TGF-{beta} signalling. We developed pancreatic cancer cell lines stably invalidated for TGF-{beta}RII and studied the impact on biological properties of pancreatic cancer cells both in vitro and in vivo. We show that TGF-{beta}RII silencing alters tumor growth and migration as well as resistance to. TGF-{beta}RII silencing also leads to S727 STAT3 and S-63 c-Jun phosphorylation, decrease of MRP3 and increase of MRP4 ABC transporter expression and induction of a partial EMT phenotype.\n\nIn the future, the better understanding TGF-{beta} signaling pathways and underlying cellular mechanisms in chemoresistance to gemcitabine may bring new therapeutic tools to clinicians.

cancer biology↗