RNA-Seq of wild-type HEK293 and K562 celllines
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Richard Kumaran Kandasamy
PROVIDER: E-MTAB-3102 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1.
Rebsamen Manuele M Pochini Lorena L Stasyk Taras T de Araújo Mariana E G ME Galluccio Michele M Kandasamy Richard K RK Snijder Berend B Fauster Astrid A Rudashevskaya Elena L EL Bruckner Manuela M Scorzoni Stefania S Filipek Przemyslaw A PA Huber Kilian V M KV Bigenzahn Johannes W JW Heinz Leonhard X LX Kraft Claudine C Bennett Keiryn L KL Indiveri Cesare C Huber Lukas A LA Superti-Furga Giulio G
Nature 20150107 7544
Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H(+)-ATPase. Her ...[more]
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Project description:Objectives: The aim of this study was to investigate the prognostic significance of thirteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. Methods: Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high resolution melting analysis and confirmed by sequencing. Results: SLC22A3 was upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC22A1 or SLC28A1was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. Conclusions: This study identified a number of associations of SLCs with prognosis of pancreatic cancer patients. Transcript levels of thirteen anticancer drug-relevant solute carrier transporters (SLCs) were determined by qPCR in pancreatic ductal adenocarcinomas and non-neoplastic tissue samples from 32 pancreatic cancer patients. MRPL19, ELF1 and POLR2A were used as reference genes for data normalization.
2013-06-30 | E-GEOD-47368 | biostudies-arrayexpress
Project description:Specific protein binders with high affinity, such as antibodies or nanobodies, are scarce for most solute carrier (SLCs) transporters. Moreover, general approaches that can systematically generate binders for multi-transmembrane proteins, such as SLCs, channels or GPCRs, are still missing. Purifying and reconstituting transmembrane proteins in their lipidic environments remain challenging, hence membrane proteins normally act as poor input material for binder generation. To overcome this challenge, we first identified state-of-the-art methods to generate protein binders targeting membrane transporters. Next, we produced full length protein or cell lines as input material for 27 SLCs, which were then processed in the selected binder generation platforms. As a result, we obtained >300 binders for 23 SLCs, 1 SLC failed and 3 SLCs are still in process. Then we established a cell-based validation workflow using immunofluorescent and immunoprecipitation methods to process all obtained binders. To further highlight the suitability of high-performance binders as an important tool for the biomolecular characterization of SLCs, we tested whether three SLC12A6 binders could be used in a quantitative co-immunoprecipitation followed by mass spectrometry (IP-MS) approach. This initial analysis of the IP-MS dataset showed that SLC12A6 specific binders are capable of strongly enriching SLC12A6. We also showed that despite high sequence similarity, the different binders showed different binder to target ratios, indicating different affinities to SLC12A6 in cell lysates. With this work, we were able to generate easily renewable and highly specific binders against SLCs, which will greatly facilitate the study of this neglected protein family.
2024-06-17 | PXD046995 | Pride
Project description:On a daily basis, we turnover billions of apoptotic cells that are removed by professional and non-professional phagocytes1-10. While characterizing the transcriptional program of phagocytes, we discovered a novel solute carrier family (SLC) gene signature (33 SLC members) that is specifically modified during engulfment of apoptotic cells (efferocytosis) but not during antibody-mediated phagocytosis. When we assessed the functional relevance of these SLCs, we noted robust induction of an aerobic glycolysis program in engulfing phagocytes, initiated by SLC2A1-mediated glucose uptake, and suppression of oxidative phosphorylation program. Interestingly, the different steps of phagocytosis10,11, i.e. smell (‘find-me’ signals / sensing factors released by apoptotic cells), taste (phagocyte- apoptotic cell contact), and ingestion (corpse internalization), activated different molecules to promote this glycolytic process. Further, lactate, a natural by-product of aerobic glycolysis12,13, was released from engulfing phagocytes via SLC16A1, an SLC member activated after corpse uptake. While glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, the lactate released via SLC16A1 influenced the establishment of an anti-inflammatory environment. Collectively, these data reveal a novel SLC program activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake, and that glycolytic byproducts of efferocytosis can also influence other cells in the microenvironment.
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Project description:Objectives: The aim of this study was to investigate the prognostic significance of thirteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. Methods: Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high resolution melting analysis and confirmed by sequencing. Results: SLC22A3 was upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC22A1 or SLC28A1was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. Conclusions: This study identified a number of associations of SLCs with prognosis of pancreatic cancer patients.
2013-06-30 | GSE47368 | GEO
Project description:<p>Solute carrier (SLC) transporters control fluxes of nutrients and metabolites across membranes and thereby represent a critical interface between the microenvironment and cellular and subcellular metabolism. Because of substantial functional overlap, the interplay and relative contributions of SLCs in response to environmental stresses remain poorly elucidated. To infer functional relationships between SLCs and metabolites, we developed a strategy to identify SLCs able to sustain cell viability and proliferation under growth-limiting concentrations of essential nutrients. One-by-one depletion of 13 amino acids required for cell proliferation enabled gain-of-function genetic screens using a SLC-focused CRISPR/Cas9–based transcriptional activation approach to uncover transporters relieving cells from growth-limiting metabolic bottlenecks. Among the transporters identified, we characterized the cationic amino acid transporter SLC7A3 as a gene that, when up-regulated, overcame low availability of arginine and lysine by increasing their uptake, whereas SLC7A5 was able to sustain cellular fitness upon deprivation of several neutral amino acids. Moreover, we identified metabolic compensation mediated by the glutamate/aspartate transporters SLC1A2 and SLC1A3 under glutamine-limiting conditions. Overall, this gain-of-function approach using human cells uncovered functional transporter-nutrient relationships and revealed that transport activity up-regulation may be sufficient to overcome environmental metabolic restrictions.</p>
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Project description:RNA-Seq of wild-type HEK293 and K562 celllines
| PRJEB7858 | ENA
Project description:<p>The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.</p>
2021-10-15 | MTBLS1925 | MetaboLights
Project description:Transporters mediate and control the flux of molecules across compartmental membranes. The human genome encodes 1500 genes with transport functions, of which the solute carriers (SLCs) form the largest superfamily with more than 450 members. Over 250 different SLCs are expressed in a typical human cell, many exhibiting overlapping expression patterns and substrate specificities. The collective role of these often seemingly redundant transporters in defining cellular outcomes, such as cell survival, remains unclear. Here, we performed pooled combinatorial KO screens to identify genetic interactions between 258 expressed SLCs, and between a subset of SLCs and selected metabolic enzymes under different growth conditions using both CRISPR-Cas12a and -Cas9 double knockout systems in the colorectal carcinoma cell line HCT116.
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Project description:Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification, and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLCs) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially coexpress Wnt4 and Sox9. SLCs become sexually dimorphic around E12.5, progressively acquire a more Sertoli- or pregranulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Last, we found that WNT4 is a crucial regulator of the SLC lineage and is required for normal development of the rete testis. In the present study, we built a transcriptomic atlas of the entire cell population of the developing female and male gonads during the process of mouse sex determination. We identified a previously uncharacterized population of supporting-like cells (SLC) and shed light on the origin and the developmental trajectory of this important cell lineage during the process of testis and ovary development.
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Project description:As a unique population of testicular mesenchymal stromal cells, stem Leydig cells (SLCs) have shown great promise in the treatment of male hypogonadism. The therapeutic functions of MSCs are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs have not been fully studied. Here, we found that transplanted SLCs restored testicular immunological homeostasis via damage signal-triggered transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated mitochondrial transfer to macrophages. Specifically, the results showed that SLCs transplantation restored male fertility and testosterone production in an ischemia‒reperfusion injury-induced acute inflammation model. This was achieved mainly via a mechanism involving the prevention of inflammatory cascades but not the differentiation to Leydig cells (LCs), the main testosterone-producing cells. Furthermore, we identified that ROS released from activated macrophages, which are the primary testicular immunocytes, induced nanotube-mediated mitochondrial transfer from SLCs to macrophages via TRPM7. Notably, TRPM7 knockdown by interfering RNA in transplanted SLCs compromised the therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. Collectively, SLC rescued testicular damage in testicular ischemia‒reperfusion mouse models, and the damage signal activated TRPM7 signaling and induced mitochondrial transfer from SLCs to macrophages, playing important roles in the repair of SLCs. These findings provide insight into the clinical translation of SLCs and suggest that strategies targeting mitochondrial transfer may be effective treatments for patients with male hypogonadism related to immune disorders.
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