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Isolating Intestinal Stem Cells from Adult Drosophila Midguts by FACS to Study Stem Cell Behavior During Aging
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The Yun/Prohibitin complex regulates adult Drosophila intestinal stem cell proliferation through the transcription

Hang Zhao1, Lin Shi1, Zhengran Li1

  • 1College of Life Sciences, Capital Normal University, Beijing 100048, China.

Proceedings of the National Academy of Sciences of the United States of America
|February 4, 2022
PubMed

Insights

Researchers identified Yun as a key factor regulating intestinal stem cell proliferation in fruit flies. The Yun/Prohibitin complex controls cell division by influencing the E2F1 transcription factor, offering insights into stem cell control and cancer.

Area of Science:

  • Stem cell biology
  • Molecular genetics
  • Cancer research

Background:

  • Adult stem cell proliferation is crucial for tissue homeostasis but dysregulation can lead to cancer.
  • Precise control mechanisms governing stem cell proliferation are not fully understood.
  • The Prohibitin (PHB) complex is implicated in various cellular processes and diseases.

Purpose of the Study:

  • To identify novel factors regulating adult stem cell proliferation using an RNA interference screen.
  • To elucidate the molecular mechanisms controlling intestinal stem cell (ISC) proliferation in *Drosophila*.
  • To uncover regulatory pathways involved in normal and aberrant stem cell growth.

Main Methods:

  • Conducted an RNA interference (RNAi) screen in *Drosophila* intestinal stem cells (ISCs).
  • Utilized genetic and biochemical approaches to characterize the function of the identified factor, Yun.
  • Investigated the interaction of Yun with the Prohibitin (PHB) complex and its downstream targets.

Main Results:

  • Identified Yun as essential for the proliferation of both normal and transformed ISCs.
  • Demonstrated that Yun acts as a scaffold to stabilize the PHB complex.
  • Showed that the Yun/PHB complex is regulated by and acts downstream of EGFR/MAPK signaling.
  • Established that the Yun/PHB complex positively regulates E2F1 levels, controlling ISC proliferation.
  • Confirmed the evolutionary conservation of the PHB complex's role in cell proliferation.

Conclusions:

  • Uncovered a novel regulatory axis: Yun/PHB-E2F1, critical for stem cell proliferation.
  • Yun stabilizes the PHB complex, integrating EGFR/MAPK signaling to control E2F1-mediated proliferation.
  • This pathway provides new targets for understanding and potentially treating diseases associated with stem cell dysregulation, including cancer.
Keywords:
DrosophilaE2F1ProhibitinYunintestinal stem cell

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