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Transcriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (RNA-Seq Mouse)

ABSTRACT: Transcriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (RNA-Seq Mouse)

PROVIDER: PRJNA760446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15712424.fastq.gz	Fastqsanger.gz
	SRR15712425.fastq.gz	Fastqsanger.gz
	SRR15712426.fastq.gz	Fastqsanger.gz
	SRR15712427.fastq.gz	Fastqsanger.gz
	SRR15712428.fastq.gz	Fastqsanger.gz

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Transcriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation

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Project description:Molecular classification of small cell lung cancer (SCLC), a lethal and heterogeneous disease, was recently proposed based on expression of four lineage-defining transcription factors SCLC-A (ASCL1), SCLC-N (NEUROD1), SCLC-Y (YAP1), and SCLC-P (POU2F3). In this study, unsupervised clustering of genome-wide histone H3K27 acetylation profiles uncovered previously unappreciated epigenomic heterogeneity of this recalcitrant disease. Specifically, the major SCLC-A subtype, which accounts for approximately 70% of all SCLC cases, was subdivided into two new subtypes SCLC-A1 and SCLC-A2. SCLC-A1 is distinguished by the presence of super-enhancer at the NKX2-1 locus, also observed in a murine SCLC model and human SCLC specimens. We found NKX2-1, a master regulator of lung lineages as well as a critical lineage factor in central nervous system, is uniquely functionally relevant in SCLC-A1, where it maintains neural lineage rather than pulmonary epithelial identity. Through integrative proteomic, transcriptomic and cistromic analyses, we found that maintenance of this neural identity in SCLC-A1 is mediated by collaborative transcriptional activity with another neuronal transcriptional factor SOX1

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