Chao Mark P, Majeti Ravindra
Department of Medicine, Division of Hematology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA.
Exp Hematol. 2019 Mar;71:68-76. doi: 10.1016/j.exphem.2019.01.002. Epub 2019 Jan 16.
The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cell lineages in an unlimited manner while maintaining the genetic identity of the originating cell. iPSCs have been utilized to investigate both monogenic and complex genetic disorders spanning hereditary and acquired diseases. Recently, iPSCs have been utilized to model human cancer, with a specific focus on modeling conditions of malignant hematopoiesis. In addition to serving as a genetic disease model in cancer, iPSCs can also be used as a tool to address a key question in interrogating the interaction between the cancer epigenome-genome. Specifically, how does reprogramming the epigenome affect cancer phenotype and specifically malignant hematopoiesis? This review will address this question and highlight the state of the field in generating iPSCs from hematologic malignancies, key biologic insights that can be uniquely generated from cancer-derived iPSCs, and their clinical applications. Last, challenges to expanding the use of iPSC modeling in blood cancers will be discussed.
将分化的体细胞进行表观遗传重编程使其恢复多能性，从而发现了诱导多能干细胞（iPSC），这为深入了解众多遗传疾病提供了重要的生物学见解。这些见解源于iPSC的关键特性，即能够无限分化为所有细胞谱系，同时保持原始细胞的遗传特性。iPSC已被用于研究单基因和复杂的遗传疾病，涵盖遗传性和获得性疾病。最近，iPSC已被用于构建人类癌症模型，尤其专注于模拟恶性造血的情况。除了作为癌症中的遗传疾病模型外，iPSC还可作为一种工具，用于解决在探究癌症表观基因组与基因组相互作用时的一个关键问题。具体而言，表观基因组重编程如何影响癌症表型，特别是恶性造血？本综述将探讨这个问题，并重点介绍从血液系统恶性肿瘤生成iPSC的领域现状、从癌症衍生的iPSC中独特产生的关键生物学见解及其临床应用。最后，将讨论扩大iPSC模型在血癌中应用的挑战。
