RNA sequencing data of differentially treated cancer associated fibroblast, myeloid-derived supression cells, and ICC tumor cells in ICC patient
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PROVIDER: PRJNA666424 | ENA |
REPOSITORIES: ENA
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Project description:An interactive tumor microenvironment with different stromal cell types is necessary for supporting cancer stemness. Cancers with dense fibrotic stroma such as intrahepatic cholangiocarcinoma (ICC) are often highly aggressive and chemotherapy resistance. Here, we show that cancer associated fibroblasts (CAF) greatly enhances the capacity of blood CD33+ myeloid-derived suppressor cells (MDSCs) to promote stem-like properties in ICC cells and tumor growth via paracrine signaling. Mechanistically, CAF mediates hyperactivated 5-LO pathway in CD33+ MDSCs via secretion of IL-6 and IL-33, resulting in overproduction of LTB4, which acts on BLT2 to promote cancer stemness via Akt-mTOR signaling. hyperactivated 5-LO pathway are observed in tumor-infiltrating CD33+ MDSCs compared with blood counterparts from the same ICC patients. Moreover, BLT2 blockade augments chemotherapeutic efficacy in ICC PDX models. Thus, our study reveals a previously unrecognized stromal cell network in which CAF educate myeloid cells to shape the optimal supportive microenvironment for the aggressive nature of ICC.
2022-01-01 | GSE158755 | GEO
Project description:Interstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine ICC are gathered in the region of the myenteric plexus (ICC-MY) and within the deep-muscular plexus near the submucosal surface of the circular muscle layer (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. In the present study we used recently developed highly selective techniques to isolate the two classes of ICC from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. Transcriptional expression of the two functional classes was investigated using DNA microarray analysis. Keywords: comparative transcriptional profiling
2007-11-29 | GSE7809 | GEO
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Gastrointestinal stromal tumors (GIST) arise within the ICC lineage due to activating KIT/PDGFRA mutations. In this study we developed a method for isolation of human ICC by immunolabeling and fluorescence-activated cell sorting (FACS). Briefly, human gastric musculature was dissociated and incubated with antibodies against CD45, FCER1A, CD11B, KIT, and CD34. ICC (defined as HP-KIT+CD34- cells), NOT ICC (defined as HP-KIT-CD34- cells), and hematopoietic (HP) cells (defined as HP+ cells) were isolated using FACS. Microarray was performed on ICC, NOT ICC, HP+ cells, and unfractionated gastric tunica muscularis. This study utilized micorarray for the phenotypic characterization of FACS-sorted human ICC, allowing comparison of ICC to other cells of the gastric musculature, including GIST. De-identified human gastric tissues obtained as surgical excess tissue from patients undergoing bariatric operations. This study utilized oligonucleotide microarray analysis to characterize the transcriptome of FACS-sorted human ICC.
2017-02-22 | GSE77839 | GEO
Project description:Interstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine ICC are gathered in the region of the myenteric plexus (ICC-MY) and within the deep-muscular plexus near the submucosal surface of the circular muscle layer (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. In the present study we used recently developed highly selective techniques to isolate the two classes of ICC from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. Transcriptional expression of the two functional classes was investigated using DNA microarray analysis. Experiment Overall Design: ICC-DMP and ICC-MY cells were isolated from the murine small intestinal tissues and their transcriptional expression was compared with that of the tunica muscularis tissues. Transcriptional expression profiles of ICC-DMP and ICC-MY were compared to each other also.
2008-06-15 | E-GEOD-7809 | biostudies-arrayexpress
Project description:Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC), a deadly bile duct malignancy. FGFR kinase inhibitors (FGFRi) have shown promising efficacy against FGFR2+ ICC in clinical trials, leading to the regulatory approval of the ATP-competitive FGFR inhibitors, pemigatinib and infigratinib (BGJ398), for this subset of patients who failed standard treatment . However, the objective response rate (ORR) for each FGFR inhibitor (FGFRi) studied to date in FGFR2+ ICC is <45% and disease progression invariably arises within ~6-12 months. By employing high-throughput drug screens and signaling studies, we identified signaling feedback via the EGFR pathway as a major mediator of adaptive resistance to FGFR kinase inhibition in a set of patient-derived ICC models. To further gain insights into the synergistic effects of the EGFR/FGFR combination and address the mechanisms underlying the survival pathway reactivation, we performed RNA sequencing in our FGFR-driven ICC models (ICC21 and ICC10-6). For these studies, we treated FGFR2 fusion+ ICC cell lines ICC21/ICC10-6 with four conditions (DMSO/Infigratinib/Afatinib/Combo) for 4 hours followed by RNA sequencing.
2024-03-21 | E-MTAB-11324 | biostudies-arrayexpress
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 mice and shown to share other phenotypic characteristics with in-situ ICC precursors (2xSCS70 cells; Bardsley et al., Gastroenterology 2010;139:942-952). 2xSCS70 cells were also found to express the ICC marker Ano1, be able to extensively self-renew in the absence of the SV40 tsA58-TAg when cultured in NeuroCult® Neural Stem Cell Proliferation Medium (NSCPM; STEMCELL Technologies) and differentiate into Kit(+) ICC both in vitro and in vivo. Wild-type cells with Kit(low)Ano1(+)Cd44(+)Cd34(+)Insr(+)Igf1r(+) phenotype (2xSCS2F10 cells) were prospectively isolated from primary cultures of dissociated gastric muscular wall tissues from 7-day-old C57BL/6J mice by serial cloning following 150-day expansion in NSCPM containing 5% cell-free chick embryo extract (CEE; Accurate Chemical). Long-term culturing of both cell lines was associated with further decline in Kit expression while expression of Ano1 and other markers of ICC precursors was maintained. Following spontaneous transformation, both 2xSCS70 and 2xSCS2F10 cells grafted into nude mice gave rise to tumors containing Kit(+)cells and otherwise resembling gastrointestinal stromal tumors (GIST), which originate from the ICC lineage (Bardsley et al., Gastroenterology 2010;139:942-952). This study utilized oligonucleotide microarray analysis to charaterize the transcriptome of non-transformed 2xSCS70 and 2xSCS2F10 cells relative to their source tissues. Total RNA from ICC progenitor cell lines and their source tissue (gastric tunica muscularis from C57BL/6J mice (source of 2xSCS2F10 cells) and H-2Kb-tsA58 mice (source of 2xSCS70 cells) was isolated. Oligonucleotide micorarray studies were performed using 2-3 Affymetrix Mouse Genome 430.2 GeneChips per sample.
2016-02-22 | E-GEOD-60744 | biostudies-arrayexpress
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 mice and shown to share other phenotypic characteristics with in-situ ICC precursors (2xSCS70 cells; Bardsley et al., Gastroenterology 2010;139:942-952). 2xSCS70 cells were also found to express the ICC marker Ano1, to be able to extensively self-renew in the absence of the SV40 tsA58-TAg when cultured in NeuroCult® Neural Stem Cell Proliferation Medium (NSCPM; STEMCELL Technologies) and to differentiate into Kit(+) ICC both in vitro and in vivo. Wild-type cells with Kit(low)Ano1(+)Cd44(+)Cd34(+)Insr(+)Igf1r(+) phenotype (2xSCS2F10 cells) were prospectively isolated from primary cultures of dissociated gastric muscular wall tissues from 7-day-old C57BL/6J mice by serial cloning following 150-day expansion in NSCPM containing 5% cell-free chick embryo extract (CEE; Accurate Chemical). Long-term culturing of both cell lines was associated with further decline in Kit expression while expression of Ano1 and other markers of ICC precursors was maintained. Following spontaneous transformation, both 2xSCS70 and 2xSCS2F10 cells grafted into nude mice gave rise to tumors containing Kit(+)cells and otherwise resembling gastrointestinal stromal tumors (GIST), which originate from the ICC lineage (Bardsley et al., Gastroenterology 2010;139:942-952). This study utilized RNA-sequencing to complement the companion microarray study in non-transformed 2xSCS70 and 2xSCS2F10 cells. Libraries were made from total RNA isolated from ICC progenitor cell lines using the Illumina TruSeq mRNA Sample Preparation Kit v2 and sequenced on the Illumina HiSeq 2000 platform.
2016-02-22 | E-GEOD-60853 | biostudies-arrayexpress
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 mice and shown to share other phenotypic characteristics with in-situ ICC precursors (2xSCS70 cells; Bardsley et al., Gastroenterology 2010;139:942-952). 2xSCS70 cells were also found to express the ICC marker Ano1, be able to extensively self-renew in the absence of the SV40 tsA58-TAg when cultured in NeuroCult® Neural Stem Cell Proliferation Medium (NSCPM; STEMCELL Technologies) and differentiate into Kit(+) ICC both in vitro and in vivo. Wild-type cells with Kit(low)Ano1(+)Cd44(+)Cd34(+)Insr(+)Igf1r(+) phenotype (2xSCS2F10 cells) were prospectively isolated from primary cultures of dissociated gastric muscular wall tissues from 7-day-old C57BL/6J mice by serial cloning following 150-day expansion in NSCPM containing 5% cell-free chick embryo extract (CEE; Accurate Chemical). Long-term culturing of both cell lines was associated with further decline in Kit expression while expression of Ano1 and other markers of ICC precursors was maintained. Following spontaneous transformation, both 2xSCS70 and 2xSCS2F10 cells grafted into nude mice gave rise to tumors containing Kit(+)cells and otherwise resembling gastrointestinal stromal tumors (GIST), which originate from the ICC lineage (Bardsley et al., Gastroenterology 2010;139:942-952). This study utilized oligonucleotide microarray analysis to charaterize the transcriptome of non-transformed 2xSCS70 and 2xSCS2F10 cells relative to their source tissues.
2016-02-22 | GSE60744 | GEO
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 mice and shown to share other phenotypic characteristics with in-situ ICC precursors (2xSCS70 cells; Bardsley et al., Gastroenterology 2010;139:942-952). 2xSCS70 cells were also found to express the ICC marker Ano1, to be able to extensively self-renew in the absence of the SV40 tsA58-TAg when cultured in NeuroCult® Neural Stem Cell Proliferation Medium (NSCPM; STEMCELL Technologies) and to differentiate into Kit(+) ICC both in vitro and in vivo. Wild-type cells with Kit(low)Ano1(+)Cd44(+)Cd34(+)Insr(+)Igf1r(+) phenotype (2xSCS2F10 cells) were prospectively isolated from primary cultures of dissociated gastric muscular wall tissues from 7-day-old C57BL/6J mice by serial cloning following 150-day expansion in NSCPM containing 5% cell-free chick embryo extract (CEE; Accurate Chemical). Long-term culturing of both cell lines was associated with further decline in Kit expression while expression of Ano1 and other markers of ICC precursors was maintained. Following spontaneous transformation, both 2xSCS70 and 2xSCS2F10 cells grafted into nude mice gave rise to tumors containing Kit(+)cells and otherwise resembling gastrointestinal stromal tumors (GIST), which originate from the ICC lineage (Bardsley et al., Gastroenterology 2010;139:942-952). This study utilized RNA-sequencing to complement the companion microarray study in non-transformed 2xSCS70 and 2xSCS2F10 cells.
2016-02-22 | GSE60853 | GEO
Project description:Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 and 7-day-old wild-type C57BL/6J mice and shown to share other phenotypic characteristics with in-situ ICC precursors (Bardsley et al., Gastroenterology 2010;139:942-952). ICC and their precursors undergo age-related depletion in mice and humans. These changes are associated with increased protein levels for transformation-related protein 53 (TRP53). This study utilized total RNA-sequencing to investigate the effects of TRP53 upregulation by nutlin 3a treatment (control: nutlin 3b) on the transcriptome of the ICC precursor line D2211B maintained in the verified absence of the SV40 tsA58 large T antigen.
2020-08-24 | GSE139539 | GEO