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Tissue Adaptation to Environmental Cues by Symmetric and Asymmetric Division Modes of Intestinal Stem Cells

Journal

Publisher

MDPI
DOI: 10.3390/ijms21176362

Keywords

stem cell; symmetric; asymmetric divisions; gut; JNK; Drosophila; mouse; adaptive growth; regeneration; stress; aging

Funding

  1. Ligue nationale contre le cancer (LNCC doctoral grant 2018)
  2. Centre national de la recherche scientifique (CNRS)
  3. Fondation ARC pour la recherche sur le cancer [20171206145]
  4. PNR-EST ANSES & ECOPHYTO II (2017)
  5. French government, through the UCAJEDI Investments in the Future project [ANR-15-IDEX-01]

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Tissues must adapt to the different external stimuli so that organisms can survive in their environments. The intestine is a vital organ involved in food processing and absorption, as well as in innate immune response. Its adaptation to environmental cues such as diet and biotic/abiotic stress involves regulation of the proliferative rate and a switch of division mode (asymmetric versus symmetric) of intestinal stem cells (ISC). In this review, we outline the current comprehension of the physiological and molecular mechanisms implicated in stem cell division modes in the adultDrosophilamidgut. We present the signaling pathways and polarity cues that control the mitotic spindle orientation, which is the terminal determinant ensuring execution of the division mode. We review these events during gut homeostasis, as well as during its response to nutrient availability, bacterial infection, chemical damage, and aging. JNK signaling acts as a central player, being involved in each of these conditions as a direct regulator of spindle orientation. The studies of the mechanisms regulating ISC divisions allow a better understanding of how adult stem cells integrate different signals to control tissue plasticity, and of how various diseases, notably cancers, arise from their alterations.

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