Multivalent state transitions shape the intratumoral composition of small cell lung carcinoma

• DOI: 10.1126/sciadv.abp8674
• Publication Date: 2022-12-14T18:58:38Z
• Authors: Priyanka Gopal; Aaron Petty; Kevin Rogacki; Titas Bera; Rohan Bareja; Craig D. Peacock; Mohamed E. Abazeed
• Keywords: Epigenome

Studies to date have not resolved how diverse transcriptional programs contribute the intratumoral heterogeneity of small cell lung carcinoma (SCLC), an aggressive tumor associated with a dismal prognosis. Here, we identify distinct and commutable states that confer discrete functional attributes in individual SCLC tumors. We combine integrative approach comprising transcriptomes 52,975 single cells, high-resolution measurement state dynamics at single-cell level, correlative studies using treatment naïve xenografts clinical outcomes. show tumors contain distinctive proportions stable cellular are governed by bidirectional transitions. Using drugs target epigenome, reconfigure composition part altering transition rates. Our results reveal new insights into behaviors promote equilibrium suggest facile plasticity underlies its resistance therapy lethality.