加拿大卡尔加里大学Marco Gallo，加拿大疾病儿童医院Michael D. Taylor和加拿大吉尔大学Nada Jabado共同合作，近期取得重要工作进展。他们研究提出，PFA室管膜瘤的三维基因组存在B型超远程相互作用（TULIP），相关研究成果2024年7月9日在线发表于《细胞》杂志上。
据介绍，颅后窝A组室管膜瘤（PFA）是一种致命的癌症，诊断于婴幼儿。由于PFA线性基因组中缺乏驱动因素事件，研究人员只能通过搜索其3D基因组以寻找特征。
研究人员重建了不同儿童肿瘤类型的3D基因组，并揭示了PFA的全局拓扑结构，这让人高度联想到各种人类组织中的干细胞和祖细胞。PFA独有的一个显著特征是PFA中的TULIP，这些区域沿着线性基因组相距很远，在3D核空间中以惊人的强度相互作用。TULIP发生在所有PFA样本中，并在可预测的基因组坐标上重复出现，它们的形成是由EZHIP的表达诱导的。
总之，TULIP在PFA样本中的普遍性表明了一种分子原理的保守性，可以在治疗中加以利用。
附：英文原文
Title: TULIPs decorate the three-dimensional genome of PFA ependymoma
Author: Michael J. Johnston, John J.Y. Lee, Bo Hu, Ana Nikolic, Elham Hasheminasabgorji, Audrey Baguette, Seungil Paik, Haifen Chen, Sachin Kumar, Carol C.L. Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel Antony Michealraj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Craig Daniels, Amulya Nageswara Rao, Caterina Giannini, Eric M. Thompson, Miklos Garami, Peter Hauser, Timea Pocza, Young Shin Ra, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa Grajkowska, Marta Perek-Polnik, Sameer Agnihotri, Stephen Mack, Benjamin Ellezam, Alex Weil, Jeremy Rich, Guillaume Bourque, Jennifer A. Chan, V. Wee Yong, Mathieu Lupien, Jiannis Ragoussis, Claudia Kleinman, Jacek Majewski, Mathieu Blanchette, Nada Jabado, Michael D. Taylor
Issue&Volume: 2024-07-09
Abstract: Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.
DOI: 10.1016/j.cell.2024.06.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00697-4