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A hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila

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  • Xingting Guo

    (National Institute of Biological Sciences
    Tsinghua University)

  • Yongchao Zhang

    (National Institute of Biological Sciences
    Tsinghua University)

  • Huanwei Huang

    (National Institute of Biological Sciences
    Tsinghua University)

  • Rongwen Xi

    (National Institute of Biological Sciences
    Tsinghua University)

Abstract

Enteroendocrine cells (EEs) represent a heterogeneous cell population in intestine and exert endocrine functions by secreting a diverse array of neuropeptides. Although many transcription factors (TFs) required for specification of EEs have been identified in both mammals and Drosophila, it is not understood how these TFs work together to generate this considerable subtype diversity. Here we show that EE diversity in adult Drosophila is generated via an “additive hierarchical TF cascade”. Specifically, a combination of a master TF, a secondary-level TF and a tertiary-level TF constitute a “TF code” for generating EE diversity. We also discover a high degree of post-specification plasticity of EEs, as changes in the code—including as few as one distinct TF—allow efficient switching of subtype identities. Our study thus reveals a hierarchically-organized TF code that underlies EE diversity and plasticity in Drosophila, which can guide investigations of EEs in mammals and inform their application in medicine.

Suggested Citation

  • Xingting Guo & Yongchao Zhang & Huanwei Huang & Rongwen Xi, 2022. "A hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34270-0
    DOI: 10.1038/s41467-022-34270-0
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    References listed on IDEAS

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    1. Craig A. Micchelli & Norbert Perrimon, 2006. "Evidence that stem cells reside in the adult Drosophila midgut epithelium," Nature, Nature, vol. 439(7075), pages 475-479, January.
    2. Benjamin Ohlstein & Allan Spradling, 2006. "The adult Drosophila posterior midgut is maintained by pluripotent stem cells," Nature, Nature, vol. 439(7075), pages 470-474, January.
    3. Guonan Lin & Na Xu & Rongwen Xi, 2008. "Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells," Nature, Nature, vol. 455(7216), pages 1119-1123, October.
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    1. Xingting Guo & Chenhui Wang & Yongchao Zhang & Ruxue Wei & Rongwen Xi, 2024. "Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Junjun Gao & Song Zhang & Pan Deng & Zhigang Wu & Bruno Lemaitre & Zongzhao Zhai & Zheng Guo, 2024. "Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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