title: The Super Elongation Complex Drives Neural Stem Cell Fate Commitment.
abstract: Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. SEC inactivation leads to neuroblast loss, whereas its forced activation results in neural progenitor dedifferentiation and tumorigenesis. Our studies unveil an SEC-mediated intracellular amplifier mechanism in ensuring robustness and precision in stem cell fate commitment and provide mechanistic explanation for the highly frequent association of SEC overactivation with human cancers.
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Shen
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Shihong M
authors.initials: SM
authors.lastname: Gao
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chouin
authors.initials: C
authors.lastname: Wong
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Feng
authors.affiliation: Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: yan.song@pku.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D021122:Protein Subunits; D051880:Receptors, Notch
keywords: Drosophila melanogaster; Notch signaling; SEC; cell fate commitment; cell fate decision; neural stem cell; neuroblast; progenitor dedifferentiation; super elongation complex; transcription elongation; tumorigenesis