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| Status |
Public on Sep 17, 2019 |
| Title |
Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abnormal differentiation contributes to the spectrum of aberrant properties of tumor cells. Differentiation of both normal and tumor cells is controlled by regulatory networks enforced by transcription factors (TFs) involved in lineage specification. Among them, pioneer factors such as FOXA1/2, are able to bind and make accessible naïve chromatin, thus critically contributing to the establishment of gene regulatory networks. Pancreatic ductal adenocarcinoma (PDAC) is characterized by massive heterogeneity, with the coexistence at all disease stages of well- and poorly-differentiated cells with diverging transcriptional networks. We found that FOXA2, a TF controlling pancreas specification, was expressed in both well- and poorly-differentiated PDAC cells, but it controlled distinct gene expression programs and displayed extensively different genomic distributions because of its partnership with TFs expressed in a differentiation grade-specific manner, such as HNF1 and HOXB8/9 in well- and poorly-differentiated cells, respectively. These data suggest that pioneer TFs such as FOXA2 are versatile transcriptional regulators whose broad contribution to the gene regulatory networks of highly heterogeneous cancers such as PDACs, depends on the differential availability of partner TFs expressed in distinct tumor cells.
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| Overall design |
Total RNA from human pancreatic ductal adenocarcinoma cell lines was processed for multiparallel sequencing. Experiments were carried out in genome edited PANC1 cell line (3 FOXA2-deleted CRISPR-Cas9 bulk cell lines and 3 wt bulk) and CFPAC1 cell line silenced with Control-siRNA, FOXA1 and/or FOXA2 siRNA.
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| Contributor(s) |
Balestrieri C, Milan M, Natoli G |
| Citation(s) |
31531882 |
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| Submission date |
Sep 13, 2018 |
| Last update date |
Oct 16, 2019 |
| Contact name |
Chiara Balestrieri |
| E-mail(s) |
balestrieri.c@gmail.com
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| Organization name |
IRCCS San Raffaele Scientific Institute
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| Department |
Center for Omics Sciences
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| Street address |
Via Olgettina 58
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| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE120017 |
Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells |
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| Relations |
| BioProject |
PRJNA490732 |
| SRA |
SRP161699 |
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