Beclin-1-dependent autophagy, but not apoptosis, is critical for stem-cell-mediated endometrial programming and the establishment of pregnancy

Pooja Popli, Suni Tang, Sangappa B. Chadchan, Chandni Talwar, Edmund B. Rucker, Xiaoming Guan, Diana Monsivais, John P. Lydon, Christina L. Stallings, Kelle H. Moley, Ramakrishna Kommagani

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The human endometrium shows a remarkable regenerative capacity that enables cyclical regeneration and remodeling throughout a woman's reproductive life. Although early postnatal uterine developmental cues direct this regeneration, the vital factors that govern early endometrial programming are largely unknown. We report that Beclin-1, an essential autophagy-associated protein, plays an integral role in uterine morphogenesis during the early postnatal period. We show that conditional depletion of Beclin-1 in the uterus triggers apoptosis and causes progressive loss of Lgr5+/Aldh1a1+ endometrial progenitor stem cells, with concomitant loss of Wnt signaling, which is crucial for stem cell renewal and epithelial gland development. Beclin-1 knockin (Becn1 KI) mice with disabled apoptosis exhibit normal uterine development. Importantly, the restoration of Beclin-1-driven autophagy, but not apoptosis, promotes normal uterine adenogenesis and morphogenesis. Together, the data suggest that Beclin-1-mediated autophagy acts as a molecular switch that governs the early uterine morphogenetic program by maintaining the endometrial progenitor stem cells.

Original languageEnglish
Pages (from-to)885-897.e4
JournalDevelopmental cell
Volume58
Issue number10
DOIs
StatePublished - May 22 2023

Keywords

  • Beclin-1
  • autophagy
  • endometrium
  • morphogenesis
  • stem cells

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