Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium.

Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium.
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单细胞转录组学分析揭示了小鼠食管上皮细胞的多样性。

DOI:
10.1038/s41467-022-29747-x
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发表时间:
2022-04-20
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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虽然形态学进展加上特定分子标记物的表达已被表征为沿着食管鳞状细胞分化梯度,分子异质性内细胞类型沿着这一轨迹尚未被分类在单细胞水平。为了解决这一知识缺口,我们对44,679只小鼠食管上皮进行了单细胞RNA测序,以确定11个不同的细胞群以及沿着基底-浅表轴和每个个体群体中的通路改变。我们评估了年龄对食管上皮细胞群的影响,并证明了年龄相关的线粒体功能障碍。我们比较了3D小鼠类器官和人食管活检组织中的单细胞转录组学特征与小鼠食管上皮的单细胞转录组学特征。最后,我们采用伪时间轨迹分析,以开发一个工作模型的细胞命运决定在小鼠食管上皮。这些研究提供了全面的分子视角的细胞异质性的小鼠食管上皮细胞的稳态和老化的背景下。食管上皮细胞多样性的水平尚未在单细胞水平上进行分类。在这里,作者分析了44,679只小鼠食管角化细胞的转录组,以确定意想不到的细胞异质性水平。
Although morphologic progression coupled with expression of specific molecular markers has been characterized along the esophageal squamous differentiation gradient, the molecular heterogeneity within cell types along this trajectory has yet to be classified at the single cell level. To address this knowledge gap, we perform single cell RNA-sequencing of 44,679 murine esophageal epithelial, to identify 11 distinct cell populations as well as pathways alterations along the basal-superficial axis and in each individual population. We evaluate the impact of aging upon esophageal epithelial cell populations and demonstrate age-associated mitochondrial dysfunction. We compare single cell transcriptomic profiles in 3D murine organoids and human esophageal biopsies with that of murine esophageal epithelium. Finally, we employ pseudotemporal trajectory analysis to develop a working model of cell fate determination in murine esophageal epithelium. These studies provide comprehensive molecular perspective on the cellular heterogeneity of murine esophageal epithelium in the context of homeostasis and aging. The level of cellular diversity in the esophageal epithelium has yet to be classified at the single cell level. Here the authors analyze the transcriptome of 44,679 murine esophageal keratinocytes to identify an unexpected level of cellular heterogeneity.
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期刊: Science (New York, N.Y.)
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