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Series GSE43252 Query DataSets for GSE43252
Status Public on Apr 09, 2013
Title Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Tissue-specific differentiation programs become dysregulated during cancer evolution. The transcription factor Nkx2-1 is a master regulator of pulmonary differentiation that is downregulated in poorly differentiated lung adenocarcinoma. Here we use conditional murine genetics to study the fate of lung epithelial cells upon loss of their master cell fate regulator. Nkx2-1 deletion in normal and neoplastic lung causes not only loss of pulmonary identity but also gastric transdifferentiation. Nkx2-1 maintains pulmonary identity by sequestering the Foxa1 transcription factor at lung-specific loci and by inhibiting Foxa1 binding to gastrointestinal targets. Murine Nkx2-1-negative lung tumors mimic the mucinous subtype of human lung adenocarcinoma, which also exhibits gastric transdifferentiation. Nkx2-1-negative lung adenocarcinomas are dependent on the gastrointestinal gene Hnf4a for efficient initiation. Thus, loss of Nkx2-1 causes transdifferentiation rather than stable dedifferentiation in vivo, suggesting that inactivation of both active and latent differentiation programs are required for tumors to reach a primitive, dedifferentiated state.
Overall design ChIP-seq data from murine lung adenocarcinomas on (i) transcription factors Nkx2-1 and Foxa in Nkx2-1-deleted tumors and Nkx2-1-positive control tumors, and (ii) four histone marks in Nkx2-1-deleted tumors and Nkx2-1-positive control tumors. (All samples in duplicate and with input controls, i.e. (2 x [(3+3) + (2+8)]) - 1 = 31 samples total - 1 input control used for transcription factor and histone mark, GSM1059357)
Contributor(s) Snyder EL, Watanabe H, Magendantz M, Hoersch S, Chen TA, Wang DG, Crowley D, Whittaker CA, Meyerson M, Kimura S, Jacks T
Citation(s) 23523371
Submission date Jan 02, 2013
Last update date May 15, 2019
Contact name Sebastian Hoersch
Organization name Massachusetts Institute of Technology
Department David H. Koch Institute for Integrative Cancer Research at MIT
Lab Bioinformatics and Computing Core
Street address 77 Massachusetts Avenue (E18-366)
City Cambridge
State/province MA
ZIP/Postal code 02474
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (31)
GSM1059354 Transcription factor #1: Nkx2-1, rep. #1
GSM1059355 Transcription factor #1: Nkx2-1, rep. #2
GSM1059356 Transcription factor #1: input, rep. #1
SRA SRP017753
BioProject PRJNA185285

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Supplementary file Size Download File type/resource
GSE43252_RAW.tar 13.5 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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