Direct Comparison of Four Hematopoietic Differentiation Methods from Human Induced Pluripotent Stem Cells
Direct Comparison of Four Hematopoietic Differentiation Methods from Human Induced Pluripotent Stem Cells
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DOI：
10.1016/j.stemcr.2020.07.009
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发表时间：
2020-09-08
影响因子：
5.9
通讯作者：
Molloy, Timothy J.
中科院分区：
文献类型：
--
作者：
Tursky, Melinda L.;Loi, To Ha;Molloy, Timothy J.
诱导多能干细胞（iPSC）是研究人类疾病的宝贵资源。然而，没有标准化的方法用于分化成造血细胞，并且缺乏对不同方法的可靠的直接比较。在目前的研究中，我们改进了一种无饲养层、无血清的方法，用于从iPSC中产生造血细胞，并将其与其他三种常用的策略在效率、可重复性、动手时间和成本方面进行了直接比较。我们还研究了他们的能力和敏感性模型遗传造血系统疾病的细胞来源于唐氏综合征和β地中海贫血患者。在这些方法中，结合芳烃受体超活化的基于多步单层的方法（“2D-多步”）是最有效的，产生了显著更高数量的CD 34（+）祖细胞和功能性造血祖细胞，同时是最具时间和成本效益的，并且最准确地再现了唐氏综合征和β-地中海贫血的表型。
Induced pluripotent stem cells (iPSCs) are an invaluable resource for the study of human disease. However, there are no standardized methods for differentiation into hematopoietic cells, and there is a lack of robust, direct comparisons of different methodologies. In the current study we improved a feeder-free, serum-free method for generation of hematopoietic cells from iPSCs, and directly compared this with three other commonly used strategies with respect to efficiency, repeatability, hands-on time, and cost. We also investigated their capability and sensitivity to model genetic hematopoietic disorders in cells derived from Down syndrome and beta-thalassemia patients. Of these methods, a multistep monolayer-based method incorporating aryl hydrocarbon receptor hyperactivation ("2D-multistep") was the most efficient, generating significantly higher numbers of CD34(+) progenitor cells and functional hematopoietic progenitors, while being the most timeand cost-effective and most accurately recapitulating phenotypes of Down syndrome and beta-thalassemia.