果蝇肠内分泌细胞的细胞多样性和转录因子编码。

The Cellular Diversity and Transcription Factor Code of Drosophila Enteroendocrine Cells.

机构信息

National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.

Peking University School of Life Sciences, Beijing 100091, China.

出版信息

Cell Rep. 2019 Dec 17;29(12):4172-4185.e5. doi: 10.1016/j.celrep.2019.11.048.

DOI:10.1016/j.celrep.2019.11.048

PMID:31851941

Abstract

Enteroendocrine cells (EEs) in the intestinal epithelium have important endocrine functions, yet this cell lineage exhibits great local and regional variations that have hampered detailed characterization of EE subtypes. Through single-cell RNA-sequencing analysis, combined with a collection of peptide hormone and receptor knockin strains, here we provide a comprehensive analysis of cellular diversity, spatial distribution, and transcription factor (TF) code of EEs in adult Drosophila midgut. We identify 10 major EE subtypes that totally produced approximately 14 different classes of hormone peptides. Each EE on average co-produces approximately 2-5 different classes of hormone peptides. Functional screen with subtype-enriched TFs suggests a combinatorial TF code that controls EE cell diversity; class-specific TFs Mirr and Ptx1 respectively define two major classes of EEs, and regional TFs such as Esg, Drm, Exex, and Fer1 further define regional EE identity. Our single-cell data should greatly facilitate Drosophila modeling of EE differentiation and function.

摘要

肠内分泌细胞（EEs）在肠道上皮中具有重要的内分泌功能，但这种细胞谱系存在很大的局部和区域差异，这阻碍了对 EE 亚型的详细特征描述。通过单细胞 RNA 测序分析，结合肽激素和受体敲入品系的收集，我们在这里对成年果蝇中肠的 EE 细胞的多样性、空间分布和转录因子（TF）编码进行了全面分析。我们鉴定出 10 种主要的 EE 亚型，它们总共产生了大约 14 种不同类别的激素肽。每个 EE 平均共产生大约 2-5 种不同类别的激素肽。对亚型富集的 TF 进行功能筛选表明，组合 TF 编码控制 EE 细胞的多样性；特定于类的 TF Mirr 和 Ptx1 分别定义了两种主要的 EE 类型，区域 TF，如 Esg、Drm、Exex 和 Fer1 进一步定义了区域 EE 身份。我们的单细胞数据应极大地促进果蝇 EE 分化和功能的建模。