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Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing.
Cell Reports ( IF 7.5 ) Pub Date : 2020-03-24 , DOI: 10.1016/j.celrep.2020.03.004 Allison M Greaney 1 , Taylor S Adams 2 , Micha Sam Brickman Raredon 3 , Elise Gubbins 4 , Jonas C Schupp 2 , Alexander J Engler 1 , Mahboobe Ghaedi 5 , Yifan Yuan 5 , Naftali Kaminski 2 , Laura E Niklason 6
Cell Reports ( IF 7.5 ) Pub Date : 2020-03-24 , DOI: 10.1016/j.celrep.2020.03.004 Allison M Greaney 1 , Taylor S Adams 2 , Micha Sam Brickman Raredon 3 , Elise Gubbins 4 , Jonas C Schupp 2 , Alexander J Engler 1 , Mahboobe Ghaedi 5 , Yifan Yuan 5 , Naftali Kaminski 2 , Laura E Niklason 6
Affiliation
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Cell-based therapies have shown promise for treating myriad chronic pulmonary diseases through direct application of epithelial progenitors or by way of engineered tissue grafts or whole organs. To elucidate environmental effects on epithelial regenerative outcomes in vitro, here, we isolate and culture a population of pharmacologically expanded basal cells (peBCs) from rat tracheas. At peak basal marker expression, we simultaneously split peBCs into four in vitro platforms: organoid, air-liquid interface (ALI), engineered trachea, and engineered lung. Following differentiation, these samples are evaluated using single-cell RNA sequencing (scRNA-seq) and computational pipelines are developed to compare samples both globally and at the population level. A sample of native rat tracheal epithelium is also evaluated by scRNA-seq as a control for engineered epithelium. Overall, this work identifies platform-specific effects that support the use of engineered models to achieve the most physiologic differential outcomes in pulmonary epithelial regenerative applications.
中文翻译：
通过单细胞 RNA 测序评估平台对肺基底细胞再生的影响。
基于细胞的疗法已显示出通过直接应用上皮祖细胞或通过工程组织移植或整个器官来治疗多种慢性肺部疾病的前景。为了阐明环境对体外上皮再生结果的影响，我们从大鼠气管中分离并培养了一群药理学扩增的基底细胞（peBC）。在基础标记物表达达到峰值时，我们同时将 peBC 分成四个体外平台：类器官、气液界面 (ALI)、工程气管和工程肺。分化后，使用单细胞 RNA 测序 (scRNA-seq) 评估这些样本，并开发计算管道以在全球和群体水平上比较样本。还通过 scRNA-seq 评估天然大鼠气管上皮样本，作为工程化上皮细胞的对照。总体而言，这项工作确定了平台特异性效应，支持使用工程模型在肺上皮再生应用中实现最具生理差异的结果。
更新日期：2020-03-26
中文翻译：
通过单细胞 RNA 测序评估平台对肺基底细胞再生的影响。
基于细胞的疗法已显示出通过直接应用上皮祖细胞或通过工程组织移植或整个器官来治疗多种慢性肺部疾病的前景。为了阐明环境对体外上皮再生结果的影响，我们从大鼠气管中分离并培养了一群药理学扩增的基底细胞（peBC）。在基础标记物表达达到峰值时，我们同时将 peBC 分成四个体外平台：类器官、气液界面 (ALI)、工程气管和工程肺。分化后，使用单细胞 RNA 测序 (scRNA-seq) 评估这些样本，并开发计算管道以在全球和群体水平上比较样本。还通过 scRNA-seq 评估天然大鼠气管上皮样本，作为工程化上皮细胞的对照。总体而言，这项工作确定了平台特异性效应，支持使用工程模型在肺上皮再生应用中实现最具生理差异的结果。
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