Studying leukemia stem cell properties and vulnerabilities with human iPSCs.
Studying leukemia stem cell properties and vulnerabilities with human iPSCs.
复制标题
DOI：
10.1016/j.scr.2020.102117
复制
发表时间：
2020-12-10
影响因子：
1.2
通讯作者：
Papapetrou EP
中科院分区：
文献类型：
--
作者：
Spyrou N;Papapetrou EP
将癌细胞重编程为诱导多能干细胞（iPSC）可以捕获整个癌症基因组，从而创建遗传上忠实的人类癌症模型。通过提供严格的遗传克隆条件，iPSC建模还可以揭示癌症异质性的非遗传来源，并提供一个独特的机会，将它们与遗传来源分开研究，正如我们最近在基于iPSC的急性髓性白血病（AML）模型中所展示的那样。来源于AML患者的遗传克隆iPSC在造血分化后复制具有白血病干细胞（LSC）层级的所有标志的表型和功能异质性。在这里，我们讨论了从iPSC建模中可以学到的关于LSC状态，其可塑性，稳定性以及遗传和表观遗传决定因素的经验教训。我们还讨论了利用AML-iPSC前瞻性分离大量iLSC用于大规模实验（如筛选）和发现AML LSC特异性新治疗靶点的实际和翻译意义。
The reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) can capture entire cancer genomes, and thus create genetically faithful models of human cancers. By providing stringent genetically clonal conditions, iPSC modeling can also unveil non-genetic sources of cancer heterogeneity and provide a unique opportunity to study them separately from genetic sources, as we recently showed in an iPSC-based model of acute myeloid leukemia (AML). Genetically clonal iPSCs, derived from a patient with AML, reproduce, upon hematopoietic differentiation, phenotypic and functional heterogeneity with all the hallmarks of a leukemia stem cell (LSC) hierarchy. Here we discuss the lessons that can be learned about the LSC state, its plasticity, stability and genetic and epigenetic determinants from iPSC modeling. We also discuss the practical and translational implications of exploiting AML-iPSCs to prospectively isolate large numbers of iLSCs for large-scale experiments, such as screens, and for discovery of new therapeutic targets specific to AML LSCs.
登录
查看更多内容
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
120.7
作者：
Gentles, Andrew J.;Plevritis, Sylvia K.;Majeti, Ravindra;Alizadeh, Ash A.
通讯作者：
Alizadeh, Ash A.
影响因子：
82.9
作者：
Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
50.3
作者：
Goardon, Nicolas;Marchi, Emanuele;Vyas, Paresh
通讯作者：
Vyas, Paresh
影响因子：
20.3
作者：
Amabile, Giovanni;Welner, Robert S.;Tenen, Daniel G.
通讯作者：
Tenen, Daniel G.