Genome-wide RNAi screen identifies networks involved in intestinal stem cell regulation in Drosophila.

Xiankun Zeng,Ying Liu,Wei Liu,Steven X Hou,Xinhua Lin,Ralph A Neumüller,Shree Ram Singh,Yanhui Hu,Lili Han,Dong Yan,Hanhan Liu

doi:10.1016/j.celrep.2015.01.051

Abstract

The intestinal epithelium is the most rapidly self-renewingtissue in adult animals and maintained by intestinal stem cells (ISCs) in both Drosophila and mammals. To comprehensively identify genes and pathways that regulate ISC fates, we performed agenome-wide transgenic RNAi screen in adult Drosophila intestine and identified 405 genes that regulate ISC maintenance and lineage-specific differentiation. By integrating these genes into publicly available interaction databases, we further developed functional networks that regulate ISC self-renewal, ISC proliferation, ISC maintenance of diploid status, ISC survival, ISC-to-enterocyte (EC) lineage differentiation, and ISC-to-enteroendocrine (EE) lineage differentiation. By comparing regulators among ISCs, female germline stem cells, and neural stem cells, we found that factors related to basic stem cell cellular processes are commonly required in all stem cells, and stem-cell-specific, niche-related signals are required only in the unique stem cell type. Our findings provide valuable insights into stem cell maintenance and lineage-specific differentiation.

Highlights

Animal tissues and organs are generated and maintained by stem cells
To identify candidate genes involved in intestinal stem cells (ISCs) regulation, we generated green fluorescent protein (GFP)-marked cells that expressed UAS-RNA interference (RNAi) in adult Drosophila intestine using esg-Gal4, UAS-GFP/+; tubGal80ts/+driver
The COPI Complex and Lipolysis—Among genes that are required for ISC survival, we identified seven components in the COPI/Arf1 (Arf79F) complex (Figures S2C-D and Table S1D), including Arf79F, Garz, and several components of the vesicle-mediated coat protein complex I (COPI) transport complex (Figures S2C-D and Table S1D)

Summary

Introduction

Animal tissues and organs are generated and maintained by stem cells During development, they generate most of the cell types to form an organ, while in adult animals they maintain tissue homeostasis by supplying new cells to replace dying or damaged ones. They generate most of the cell types to form an organ, while in adult animals they maintain tissue homeostasis by supplying new cells to replace dying or damaged ones To accomplish this task, stem cells have to continuously renew themselves and, at the same time, generate daughter cells to produce terminal differentiated cells for their organ-specific functions. The somatic differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) through overexpression of a few transcription factors or the metabolic switch (Ito and Suda, 2014; Takahashi and Yamanaka, 2006; Zhang et al, 2012). Understanding how adult stem cells ( somatic adult stem cells) are regulated is important for understanding tissue degeneration and tumorigenesis

Results

Discussion

Conclusion