Dr. Rongwen Xi’s lab provides insights into the cellular diversity of enteroendocrine cells

On December 17th, 2019, Dr. Rongwen Xi‘s lab published an article entitled “The Cellular Diversity and Transcription Factor Code of Drosophila Enteroendocrine Cells.” in journal Cell Reports. This article systematically characterized the cellular diversity, spatial distribution and transcription factor code of enteroendocrine cells in Drosophila, which reveals new insights into the cellular diversity of enteroendocrine cells and should greatly facilitate further Drosophila modeling of enteroendocrine cell regulation and function.

Enteroendocrine cells (EEs) are scattered along the length of the intestine and have important endocrine functions, yet this cell lineage exhibits great local and regional variations, which hampers detailed characterization of EE subtypes. In this article, the authors described a comprehensive analysis of cellular diversity, spatial distribution and associated transcription factor code of EEs in adult Drosophila midgut through single cell RNA-sequencing analysis, combined with a region- specific gene enrichment algorithm and a collection of neuropeptide/receptor knock-in strains (the chemoconnectome CCT lines) .

Figure 1. Ten mature EE subtypes revealed by scRNA-seq.

The major findings from this study include: 1. Ten major EE subtypes have been identified that totally produce 14 different classes of neuropeptide genes; 2. Each EE on average co-produces 2-5 different classes of peptide hormones, with 8 by maximum; 3. The EE subtypes are spatially mapped using a new algorithm and confirmed by the CCT lines; 4. Analysis of hormone receptors expressed in EEs reveals potential paracrine and long-range signaling mechanisms among EE subtypes; 5. The transcription factor code for each EE subtypes is determined; 6. Genetic screens with the candidate TFs identify class-specific TFs that respectively specify Tk⁺ class II and AstC⁺ class I EEs, and region-specific TFs that define regional EE identity.

Figure 2. EE subtypes and their spatial distribution.

These findings support a TF code hypothesis in which a combination of class-specific TFs (via Notch signaling) and region-specific TFs (determined by A/P axis body patterning) collectively define the cellular diversity of enteroendocrine cells. Therefore, these findings provide new insights into enteroendocrine cell diversity and its fate control mechanisms. In addition, the single-cell data generated in this study along with the established online searchable database (FlyEE-seq: https://xilab.shinyapps.io/database/) should serve as an invaluable resource for further understanding the regulation and function of enteroendocrine cells.

Figure 3. The transcription factor code for EE subtypes.

Drs. Xingting Guo, Chang Yin and Fu Yang, and Yongchao Zhang from Dr, Rongwen Xi lab are co-first authors of this paper. Other contributors include Huanwei Huang, Jiawen Wang and Dr. Tao Cai from NIBS sequencing center, and Drs. Bowen Deng and Yi Rao from Peking University School of Life Sciences. Dr. Rongwen Xi is the corresponding author. The work was supported by the Ministry of Science and Technology of China and Beijing Municipal Government, and was carried out at the National Institute of Biological Sciences, Beijing.