Capybara: A computational tool to measure cell identity and fate transitions.
Capybara: A computational tool to measure cell identity and fate transitions.
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DOI：
10.1016/j.stem.2022.03.001
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发表时间：
2022-04-07
期刊：
影响因子：
23.9
通讯作者：
A. Morris, Samantha
中科院分区：
文献类型：
--
作者：
Kong, Wenjun;C. Fu, Yuheng;Holloway, Emily M.;Garipler, Gorkem;Yang, Xue;Mazzoni, Esteban O.;A. Morris, Samantha
由于细胞类型和状态不断转变，测量发育、疾病和重编程中的细胞身份具有挑战性。在这里，我们提出了 Capybara，一种计算工具，用于对离散细胞身份和中间“混合”细胞状态进行分类，支持量化细胞命运转变动态的指标。我们使用实验谱系追踪数据验证杂交细胞，以证明这些中间细胞状态的多谱系潜力。我们应用水豚来诊断几种细胞工程方案中的缺陷，识别心脏重编程中的混合状态和运动神经元编程中的脱靶身份，我们通过添加外源信号因子来缓解这些缺陷。此外，我们建立了诱导内胚层祖细胞的假定体内相关性，迄今为止，这种细胞类型的定义仍不明确。总之，这些结果展示了水豚在剖析细胞身份和命运转变方面的实用性，优先考虑干预措施以提高干细胞工程的效率和保真度。孔等人。目前 Capybara 是一种计算管道，用于对离散细胞身份和中间“混合”细胞状态进行分类。他们应用水豚来诊断多种细胞工程方案中的缺陷，识别心脏重编程中的混合状态和运动神经元编程中的脱靶神经身份，从而改进方案以提高靶细胞产量。此外，他们还证明了水豚在鉴定诱导内胚层祖细胞的体内相关性方面的效用，诱导内胚层祖细胞是直接谱系重编程的相对未表征的产物。
Measuring cell identity in development, disease, and reprogramming is challenging as cell types and states are in continual transition. Here, we present Capybara, a computational tool to classify discrete cell identity and intermediate ‘hybrid’ cell states, supporting a metric to quantify cell fate transition dynamics. We validate hybrid cells using experimental lineage tracing data to demonstrate the multi-lineage potential of these intermediate cell states. We apply Capybara to diagnose shortcomings in several cell engineering protocols, identifying hybrid states in cardiac reprogramming and off-target identities in motor neuron programming, which we alleviate by adding exogenous signaling factors. Further, we establish a putative in vivo correlate for induced endoderm progenitors, a cell type that has, to date, remained poorly defined. Together, these results showcase the utility of Capybara to dissect cell identity and fate transitions, prioritizing interventions to enhance the efficiency and fidelity of stem cell engineering. Kong et al. present Capybara, a computational pipeline to classify discrete cell identity and intermediate ‘hybrid’ cell states. They apply Capybara to diagnose shortcomings in several cell engineering protocols, identifying hybrid states in cardiac reprogramming and off-target neural identities in motor neuron programming, leading to improved protocols to increase target cell yield. Further, they demonstrate the utility of Capybara to identify an in vivo correlate for induced endoderm progenitors, a relatively uncharacterized product of direct lineage reprogramming.
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