PUBLICATION

Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance

Authors
Brock, C.K., Wallin, S.T., Ruiz, O.E., Samms, K.M., Mandal, A., Sumner, E.A., Eisenhoffer, G.T.
ID
ZDB-PUB-190406-1
Date
2019
Source
Nature communications   10: 1044 (Journal)
Registered Authors
Eisenhoffer, George, Samms, Krystin
Keywords
none
MeSH Terms
  • Animals
  • Apoptosis/drug effects
  • Apoptosis/physiology
  • Caspases/metabolism
  • Cell Division/drug effects
  • Cell Division/physiology
  • Cell Proliferation/physiology
  • Cytoskeletal Proteins/metabolism
  • Embryo, Nonmammalian
  • Epithelial Cells/drug effects
  • Epithelial Cells/physiology*
  • Epithelium/physiology*
  • Extracellular Vesicles/physiology*
  • Phenylurea Compounds/pharmacology
  • Signal Transduction/physiology
  • Stem Cells/drug effects
  • Stem Cells/physiology*
  • Wnt Proteins/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
  • ortho-Aminobenzoates/pharmacology
PubMed
30837472 Full text @ Nat. Commun.
Abstract
Epithelial tissues require the removal and replacement of damaged cells to sustain a functional barrier. Dying cells provide instructive cues that can influence surrounding cells to proliferate, but how these signals are transmitted to their healthy neighbors to control cellular behaviors during tissue homeostasis remains poorly understood. Here we show that dying stem cells facilitate communication with adjacent stem cells by caspase-dependent production of Wnt8a-containing apoptotic bodies to drive cellular turnover in living epithelia. Basal stem cells engulf apoptotic bodies, activate Wnt signaling, and are stimulated to divide to maintain tissue-wide cell numbers. Inhibition of either cell death or Wnt signaling eliminated the apoptosis-induced cell division, while overexpression of Wnt8a signaling combined with induced cell death led to an expansion of the stem cell population. We conclude that ingestion of apoptotic bodies represents a regulatory mechanism linking death and division to maintain overall stem cell numbers and epithelial tissue homeostasis.
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