ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/009/SRR15712409/SRR15712409_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/015/SRR15712415/SRR15712415_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/013/SRR15712413/SRR15712413_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/007/SRR15712407/SRR15712407_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/009/SRR15712409/SRR15712409_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/015/SRR15712415/SRR15712415_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/008/SRR15712408/SRR15712408_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/014/SRR15712414/SRR15712414_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/011/SRR15712411/SRR15712411_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/008/SRR15712408/SRR15712408_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/012/SRR15712412/SRR15712412_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/010/SRR15712410/SRR15712410_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/012/SRR15712412/SRR15712412_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/007/SRR15712407/SRR15712407_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/010/SRR15712410/SRR15712410_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/011/SRR15712411/SRR15712411_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/014/SRR15712414/SRR15712414_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR157/013/SRR15712413/SRR15712413_1.fastq.gzprimaryOK200GenomicsHideo Watanabe, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinaihttps://www.ebi.ac.uk/ena/browser/view/PRJNA760448Homo sapiensMolecular 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 Overall design: Transcriptomic profile of NCI-H187 cells genetically engineered to deplete the expression of SOX1 or NKX2-1 with controlxref:PubMed:35848993ENAfalseTranscriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (RNA-Seq H187)Transcriptional circuitry of NKX2-1 and SOX1 defines a previously unrecognized lineage subtype of small cell lung cancer to maintain neuroendocrine differentiation (RNA-Seq H187)2025-09-242022-10-07PRJNA760448GSE183370960635848993