@article{566eeff74e534271bc8cce2cf8c309fd,
title = "A neurodevelopmental epigenetic programme mediated by SMARCD3–DAB1–Reelin signalling is hijacked to promote medulloblastoma metastasis",
abstract = "How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly available datasets with our newly generated data reveal that SMARCD3 (also known as BAF60C) regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. We further identify that a core set of transcription factors, enhancer of zeste homologue 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the cis-regulatory elements at the SMARCD3 locus to form a chromatin hub to control SMARCD3 expression in the developing cerebellum and in metastatic MB. Increased SMARCD3 expression activates Reelin–DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for patients with MB.",
author = "Han Zou and Bradley Poore and Brown, {Emily E.} and Jieqi Qian and Bin Xie and Evridiki Asimakidou and Vladislav Razskazovskiy and Deanna Ayrapetian and Vaibhav Sharma and Shunjin Xia and Fei Liu and Apeng Chen and Yongchang Guan and Zhengwei Li and Siyi Wanggou and Olivier Saulnier and Michelle Ly and Wendy Fellows-Mayle and Guifa Xi and Tadanori Tomita and Resnick, {Adam C.} and Mack, {Stephen C.} and Raabe, {Eric H.} and Eberhart, {Charles G.} and Dandan Sun and Stronach, {Beth E.} and Sameer Agnihotri and Gary Kohanbash and Songjian Lu and Karl Herrup and Rich, {Jeremy N.} and Gittes, {George K.} and Alberto Broniscer and Zhongliang Hu and Xuejun Li and Pollack, {Ian F.} and Friedlander, {Robert M.} and Hainer, {Sarah J.} and Taylor, {Michael D.} and Baoli Hu",
note = "Funding Information: We thank R. A. DePinho and X. Wu for critically evaluating the manuscript; E. Jane, P. Daniel and D. Yimlamai for their assistance with reagents; J. Dai, X. Lin, X. Lin, T. Wu, M. Wu, J. Hu, K. Peng, Y. Li, Y. Zhang, J. Wang and D. Xing from Central South University, and X. Zheng from UPMC Children{\textquoteright}s Hospital of Pittsburgh for their technical support; J. J. Michel, M. L. Mulkeen, M. Airik, K. Prasadan, Y. Wu, A. C. Poholek, W. A. MacDonald and R. Elbakri from the core facilities at the Rangos Research Center for their assistance with flow cytometry, microscopy, mouse imaging and sequencing analyses. We gratefully acknowledge funding support from the Matthew Larson Foundation (to B.H.), the Connor{\textquoteright}s Cure Fund from the V Foundation (to B.H.), the Andrew McDonough B+ Foundation (to B.H.), the Scientific Program Fund from the Children{\textquoteright}s Hospital of Pittsburgh (to B.H.), NIH/NINDS 1R21NS125218-01 (to B.H.) and NIGMS R35GM133732 (to S.J.H.). This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. H.Z. is a University of Pittsburgh-affiliated visiting research scholar supported by CSC and Central South University. Funding Information: We thank R. A. DePinho and X. Wu for critically evaluating the manuscript; E. Jane, P. Daniel and D. Yimlamai for their assistance with reagents; J. Dai, X. Lin, X. Lin, T. Wu, M. Wu, J. Hu, K. Peng, Y. Li, Y. Zhang, J. Wang and D. Xing from Central South University, and X. Zheng from UPMC Children{\textquoteright}s Hospital of Pittsburgh for their technical support; J. J. Michel, M. L. Mulkeen, M. Airik, K. Prasadan, Y. Wu, A. C. Poholek, W. A. MacDonald and R. Elbakri from the core facilities at the Rangos Research Center for their assistance with flow cytometry, microscopy, mouse imaging and sequencing analyses. We gratefully acknowledge funding support from the Matthew Larson Foundation (to B.H.), the Connor{\textquoteright}s Cure Fund from the V Foundation (to B.H.), the Andrew McDonough B+ Foundation (to B.H.), the Scientific Program Fund from the Children{\textquoteright}s Hospital of Pittsburgh (to B.H.), NIH/NINDS 1R21NS125218-01 (to B.H.) and NIGMS R35GM133732 (to S.J.H.). This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. H.Z. is a University of Pittsburgh-affiliated visiting research scholar supported by CSC and Central South University. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = mar,
doi = "10.1038/s41556-023-01093-0",
language = "English (US)",
volume = "25",
pages = "493--507",
journal = "Nature cell biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "3",
}