biostudies-literatureZhang XMinistry of Science and Technology of the People’s Republic of ChinaTianjin Science and Technology Committee (Tianjin Municipal Science and Technology Commission)National Natural Science Foundation of ChinaMinistry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)Tianjin Science and Technology CommitteeNational Natural Science Foundation of China (National Science Foundation of China)748-759https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977910biostudies-literatureUnknown128(5)<h4>Background</h4>Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer without recognised morphologic or genetic heterogeneity. Based on the expression of four transcription factors, ASCL1, NEUROD1, POU2F3, and YAP1, SCLCs are classified into four subtypes. However, biological functions of these different subtypes are largely uncharacterised.<h4>Methods</h4>We studied intratumoural heterogeneity of resected human primary SCLC tissues using single-cell RNA-Seq. In addition, we undertook a series of in vitro and in vivo functional studies to reveal the distinct features of SCLC subtypes.<h4>Results</h4>We identify the coexistence of ASCL1⁺ and NEUROD1⁺ SCLC cells within the same human primary SCLC tissue. Compared with ASCL1⁺ SCLC cellBritish journal of cancerMolecular features and evolutionary trajectory of ASCL1⁺ and NEUROD1⁺ SCLC cells.PMC997791020JCZDJC00110818723502018YFC131300282171133428177303418JCZDJC991008182501782273119Liu ZZhang ZChen JXiao ZZhang XMa ZWang HLiu WGong WfalseMolecular features and evolutionary trajectory of ASCL1⁺ and NEUROD1⁺ SCLC cells.<h4>Background</h4>Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer without recognised morphologic or genetic heterogeneity. Based on the expression of four transcription factors, ASCL1, NEUROD1, POU2F3, and YAP1, SCLCs are classified into four subtypes. However, biological functions of these different subtypes are largely uncharacterised.<h4>Methods</h4>We studied intratumoural heterogeneity of resected human primary SCLC tissues using single-cell RNA-Seq. In addition, we undertook a series of in vitro and in vivo functional studies to reveal the distinct features of SCLC subtypes.<h4>Results</h4>We identify the coexistence of ASCL1⁺ and NEUROD1⁺ SCLC cells within the same human primary SCLC tissue. Compared with ASCL1⁺ SCLC cell2023-01-01T00:00:00Z2023 Mar2025-04-05T16:14:10.525Z2025-04-05T16:14:10.525ZS-EPMC99779103651755110.1038/s41416-022-02103-y