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SRX11361524: GSM5420551: ZR1532 [C/EBP Bulk RNA-seq]; Mus musculus; RNA-Seq
1 ILLUMINA (NextSeq 500) run: 13.2M spots, 2G bases, 688.3Mb downloads

Submitted by: NCBI (GEO)
Study: LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer [C/EBP Bulk RNA-seq]
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Background: LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. Restoration of Lkb1 in established lung tumors promotes the expression of C/EBP target genes as well as features of alveolar type II cell differentiation, which requires the activity of C/EBP transcription factors in the developmental setting. Purpose: To determine the extent to which the disruption of C/EBP transcription factors recapitulates the transcriptional changes induced by the inactivation of Lkb1.Approach: To assess the changes gene expression induced by CRISPR/Cas9-mediated disruption of either C/EBP transcription factors or Lkb1, we induced lung tumors in KrasLSL-G12D/+;R26LSL-tdTomato;H11LSL-Cas9 mice using Lenti-sgNeo1/sgNT/sgNeo2/Cre (sgInert), Lenti-sgLkb1/Cre (sgLkb1), or Lenti-sgCebpa/sgCebpb/sgCebpd/Cre (sgCebpa/b/d). Neoplastic cells were then isolated from lung tumors by FACS for gene expression profiling by RNA-seq. Results: The disruption of C/EBP transcription factors partially recapitulates the gene expression changes induced by Lkb1 inactivation. Among the genes that are jointly dependent upon C/EBP transcription factors and LKB1 is an enrichment of NKX2-1-dependent target genes. Conclusions: C/EBP transcription factors likely operate downstream of LKB1 in an indirect manner, collaborating with another key developmental regulator, NKX2-1, to enforce alveolar type II cell differentiation to constrain tumor growth. Overall design: Lung tumors were initiated in KrasLSL-G12D/+;R26LSL-tdTomato;H11LSL-Cas9 mice with Lenti-sgNeo1/sgNT/sgNeo2/Cre (sgInert), Lenti-sgLkb1/Cre (sgLkb1), or Lenti-sgCebpa/sgCebpb/sgCebpd/Cre (sgCebpa/b/d). Following tumor development, neoplastic cells were FACS-isolated from lung tumors and subjected to bulk RNA-seq.
Sample: ZR1532 [C/EBP Bulk RNA-seq]
SAMN20081419 • SRS9407879 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: NextSeq 500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Microdissected lung tumors were dissociated with collagenase IV, dispase, and trypsin at 37 °C for 30 min. After dissociation, the samples were maintained on ice, in the presence of 2 mM EDTA and 1 U/mL DNase to prevent aggregation. For the sorting of neoplastic cells, the dissociated cells were stained with antibodies against CD45 (BioLegened, 103112), CD31 (BioLegend, 303116), F4/80 (BioLegend, 123116), and Ter119 (BioLegend, 116212) to exclude hematopoietic and endothelial cells (lineage-positive (Lin+) cells). DAPI was used to exclude dead cells. FACSAria sorters (BD Biosciences) were used for cell sorting.RNA was purified using RNA/DNA Allprep kit (Qiagen, 80284). RNA quality was assessed using the RNA6000 PicoAssay for the Agilent 2100 Bioanalyzer. Two to ten nanograms of total RNA served as input for the preparation of RNA-Seq libraries using the Trio RNA-Seq, Mouse rRNA kit (Tecan Genomics: 0507-32). Libraries were constructed per the manufacturer's instructions. Purified libraries were assessed using the Agilent High Sensitivity DNA kit (Agilent Technologies: 5067-4626).
Experiment attributes:
GEO Accession: GSM5420551
Links:
Runs: 1 run, 13.2M spots, 2G bases, 688.3Mb
Run# of Spots# of BasesSizePublished
SRR1505110513,150,5072G688.3Mb2021-12-24

ID:
15181840

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