Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease.
Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease.
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DOI：
10.1016/j.devcel.2020.11.010
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发表时间：
2020-12-21
影响因子：
11.8
通讯作者：
Zilbauer M
中科院分区：
文献类型：
--
作者：
Elmentaite R;Ross ADB;Roberts K;James KR;Ortmann D;Gomes T;Nayak K;Tuck L;Pritchard S;Bayraktar OA;Heuschkel R;Vallier L;Teichmann SA;Zilbauer M
人类肠道发育需要分化细胞类型的协调相互作用。在这里，我们生成了受孕后6-10周发育中的人类肠道的深入单细胞图。我们的分析揭示了循环上皮前体细胞的转录谱;与LGR 5表达细胞不同。我们认为，这些细胞可能有助于分化的细胞亚群，通过产生LGR 5表达干细胞和接收信号，从周围的间充质细胞。此外，我们绘制了离体组织和体外胎儿类器官的转录组之间的相似之处，揭示了类器官培养物在培养皿中的成熟。最后，我们比较了来自儿科克罗恩病上皮的scRNA-seq图谱以及匹配的健康对照，以揭示上皮组成中的疾病相关变化。对比这些与胎儿的配置文件揭示了胎儿转录因子在克罗恩病的重新激活。我们的研究提供了一个资源，可在www.gutcellatlas.org，并强调了解开胎儿发育在理解疾病的重要性。发育中和儿科人类肠的单细胞RNA-seq图谱BEX 5+上皮前体细胞与成人LGR 5+干细胞不同人类胎儿肠类器官在培养中成熟胎儿转录因子在克罗恩病上皮细胞中被重新激活Elmentaite和Ross等人生成了发育中的人类肠道的详细单细胞RNA-seq图谱。数据分析揭示了早期肠上皮前体细胞的存在和胎儿转录因子在诊断为克罗恩病的儿童肠上皮中的重新激活。这项研究提供了一个独特的资源，所有研究人员都可以在www.gutcellatlas.org上访问。
Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6–10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn’s disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn’s disease. Our study provides a resource available at www.gutcellatlas.org, and underscores the importance of unraveling fetal development in understanding disease. Single-cell RNA-seq map of the developing and pediatric human intestine Cycling BEX5+ epithelial precursors are distinct from adult LGR5+ stem cells Human fetal intestinal organoids mature in culture Fetal transcription factors are reactivated in the Crohn’s disease epithelium Elmentaite and Ross et al. generated a detailed single-cell RNA-seq map of the developing human intestine. Data analyses revealed the presence of an early intestinal epithelial precursor cell and the re-activation of fetal transcription factors in the intestinal epithelium of children diagnosed with Crohn’s disease. The study provides a unique resource accessible to all researchers at www.gutcellatlas.org.
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影响因子：
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通讯作者：
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