Division of Hematology, Department of Medicine, Department of Genome Sciences, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, United States.
Division of Hematology, Department of Medicine, Department of Genome Sciences, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, United States.
Stem Cell Res. 2021 Apr;52:102195. doi: 10.1016/j.scr.2021.102195. Epub 2021 Jan 26.
Reprogramming of cells from patients with genetic disorders to pluripotency is a promising avenue to understanding disease biology. A number of induced pluripotent stem cell (iPSC) models of inherited monogenic blood disorders have been reported over the past decade. However, the application of iPSCs for modeling of hematological malignancies has only recently been explored. Blood malignancies comprise a spectrum of genetically heterogeneous disorders marked by the acquisition of somatic mutations and chromosomal aberrations. This genetic heterogeneity presents unique challenges for iPSC modeling, but also opportunities to capture genetically distinct states and generate models of stepwise progression from normal to malignant hematopoiesis. Here we briefly review the current state of this field, highlighting current models of acquired pre-malignant and malignant blood disorders and clonal evolution, and challenges including barriers to reprogramming and differentiation of iPSCs into bona fide hematopoietic stem cells.
将遗传疾病患者的细胞重新编程为多能性是了解疾病生物学的一个很有前途的途径。在过去的十年中，已经报道了许多遗传性单基因血液疾病的诱导多能干细胞（iPSC）模型。然而，iPSC 在血液恶性肿瘤模型中的应用直到最近才得到探索。血液恶性肿瘤包括一系列遗传异质性疾病，其特征是获得体细胞突变和染色体异常。这种遗传异质性对 iPSC 建模提出了独特的挑战，但也为捕捉遗传上不同的状态并生成从正常造血到恶性造血的逐步进展模型提供了机会。在这里，我们简要回顾了这一领域的现状，重点介绍了获得性前恶性和恶性血液疾病以及克隆进化的当前模型，以及包括重编程和 iPSC 分化为真正造血干细胞的障碍等挑战。
