Apical-basal polarity precisely determines intestinal stem cell number by regulating Prospero threshold

Song Wu, Yang Yang, Ruizhi Tang, Song Zhang, Peizhong Qin, Rong Lin, Neus Rafel, Elena M. Lucchetta, Benjamin Ohlstein, Zheng Guo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Apical-basal polarity and cell-fate determinants are crucial for the cell fate and control of stem cell numbers. However, their interplay leading to a precise stem cell number remains unclear. Drosophila pupal intestinal stem cells (pISCs) asymmetrically divide, generating one apical ISC progenitor and one basal Prospero (Pros)+ enteroendocrine mother cell (EMC), followed by symmetric divisions of each daughter before adulthood, providing an ideal system to investigate the outcomes of polarity loss. Using lineage tracing and ex vivo live imaging, we identify an interlocked polarity regulation network precisely determining ISC number: Bazooka inhibits Pros accumulation by activating Notch signaling to maintain stem cell fate in pISC apical daughters. A threshold of Pros promotes differentiation to EMCs and avoids ISC-like cell fate, and over-threshold of Pros inhibits miranda expression to ensure symmetric divisions in pISC basal daughters. Our work suggests that a polarity-dependent threshold of a differentiation factor precisely controls stem cell number.

Original languageEnglish (US)
Article number112093
JournalCell Reports
Volume42
Issue number2
DOIs
StatePublished - Feb 28 2023
Externally publishedYes

Keywords

  • Baz
  • CP: Cell biology
  • CP: Stem cell research
  • Mira
  • Notch activation
  • Par-6
  • Pros threshold
  • aPKC
  • apical-basal polarity
  • pupal intestinal stem cell
  • stem cell number

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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