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Series GSE213103 Query DataSets for GSE213103
Status Public on May 01, 2024
Title Transcriptional profiling of human colon “cancer stem cell” populations (EpCAM+, CD44+, CD166+) following in vivo exposure to irinotecan.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary In human colon cancer, the malignant component of tumor tissues often contains multiple sub-types of cancer cells, whose transcriptional profiles and surface marker phenotypes correspond to those of the epithelial lineages that are found in normal colonic crypts (e.g., goblet cells, enterocytes, LGR5+ columnar basal cells). Among those various sub-types of malignant cells, those characterized by a surface marker phenotype that is characteristic of epithelial stem/progenitor cells residing at the bottom of colonic crypts (EpCAM+, CD44+, CD166+) are enriched in cells with "cancer stem cell" (CSC) properties, such as self-renewal (i.e., the capacity to sustain the formation of new tumors upon serial xeno-transplantation in immune-deficient animals) and multi-lineage differentiation (i.e., the capacity to sustain the formation of other cell-types, thus reconstituting the heterogeneous population of the parent tumors from which they have been isolated). Cell populations with "cancer stem cell" (CSC) properties are known to be preferentially resistant to several cytotoxic agents used in conventional chemotherapy, but the molecular mechanisms underpinning this property remain poorly understood.

In this dataset, we report the analysis by gene-expression microarrays of the transcriptional profile of two sub-populations of human colon cancer cells: 1) cells with a "bottom-of-the-crypt" phenotype (EpCAM+, CD44+, CD166+), which are known to be enriched in "cancer stem cells" (CSCs); and 2) cells with a "top-of-the-crypt" phenotype (EpCAM+, CD44neg, CD166neg), which are known to be non-tumorigenic upon xeno-transplantation in immune-deficient mice. The two populations were purified in parallel by fluorescence activated cell sorting (FACS), starting from solid tumors established by sub-cutaneous (s.c.) engraftment in immune-deficient mice of a patient-derived xenograft (PDX) line representative of a moderately differentiated (G2) primary colon carcinoma. To identify genes whose expression is modulated by in vivo exposure to chemotherapy (and thus potentially involved in the mechanistic regulation of chemo-resistance), we compared the transcriptional profile of cells purified from tumors that were exposed to 4 weeks of in vivo treatment with either irinotecan (CPT-11) or a placebo control (saline solution).

 
Overall design The two sub-populations of colon cancer cells analyzed in this study (EpCAM+/CD44+/CD166+, EpCAM+/CD44neg/CD166neg) were isolated in parallel by fluorescence activated cell sorting (FACS), starting from solid tumors that were established by sub-cutaneous (s.c.) xeno-transplantation into adult, female, NOD/SCID/IL2Rg-/- (NSG) immune-deficient mice (The Jackson Laboratory: stock #005557) of a patient-derived xenograft (PDX) line representative of a moderately differentiated (G2) primary colon carcinoma (PDX-COLON-8), and following in vivo treatment of tumor-bearing mice with either irinotecan (50 ug/g, once weekly x 4 weeks, i.p.) or a placebo (1 ml saline solution, once weekly x 4 weeks, i.p.). The two populations of cancer cells were sorted in parallel from 4 independent tumors (2 from animals treated with irinotecan + 2 from animals treated with saline solution), for a total of 8 samples, which included 4 replicates for each of the two main orthogonal variables (cell phenotype vs. in vivo treatment). Tumor tissues were dissociated into single-cell suspensions by mechanical mincing into small fragments, followed by enzymatic digestion using DNAse-I (100 units/ml) and collagenase-III (200 units/ml), according to previously published protocols (Dalerba et al., PNAS, 104:10158-10163, 2007; Dalerba et al., Nature Biotechnology, 29:1120-1127, 2011). Single-cell suspensions were stained with monoclonal antibodies directed against differentially expressed surface antigens (human cells: EpCAM, CD44, CD166; mouse cells: H2-Kd) and sorted using a FACSAria-II machine (Becton Dickinson), after exclusion of dead cells (DAPI+), cell doublets (serial gating based on FSC-A vs. FSC-H and SSC-A vs. SSC-W profiles) and mouse cells (H2-Kd+).

 
Contributor(s) Matsubara J, Li YF, Sahoo D, Dalerba P
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Sep 11, 2022
Last update date May 01, 2024
Contact name Piero Dalerba
E-mail(s) pdd2109@columbia.edu
Organization name Columbia University
Department Pathology and Cell Biology
Lab ICRC - Room 924
Street address 1130 St. Nicholas Ave.
City New York
State/province NY
ZIP/Postal code 10032
Country USA
 
Platforms (1)
GPL15207 [PrimeView] Affymetrix Human Gene Expression Array
Samples (8)
GSM6571711 colon cancer cells, tumorigenic [EpCAM+, CD44+, CD166+], irinotecan [mouse #3727]
GSM6571712 colon cancer cells, non-tumorigenic [EpCAM+, CD44neg, CD166neg], irinotecan [mouse #3727]
GSM6571713 colon cancer cells, tumorigenic [EpCAM+, CD44+, CD166+], irinotecan [mouse #3735]
Relations
BioProject PRJNA879191

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Supplementary file Size Download File type/resource
GSE213103_RAW.tar 16.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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