Abstract
Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche.
Highlights
Stem cells have two important properties, self-renewal and differentiation, which are critical for continuously generating new functional cells to maintain tissue homeostasis
To facilitate the identification of germ line stem cell (GSC) and differentiated germ cells, spectrosomes and fusomes are labeled by Hts staining (Lin et al, 1994), and germ cells are visualized by Vasa staining (Lasko and Ashburner, 1988)
In Drosophila, Wnt ligands bind the receptor complex composed of Frizzled (Fz), Frizzled 2 (Fz2) and Arrow to activate Dsh and stabilize Arm, which forms a protein complex with a TCF (T Cell Factor)-like Pangolin in the nucleus to activate target gene expression, whereas Axin (Axn) and Shaggy (Sgg) negatively modulate Wnt signaling by promoting Arm degradation (Logan and Nusse, 2004)
Summary
Stem cells have two important properties, self-renewal and differentiation, which are critical for continuously generating new functional cells to maintain tissue homeostasis. Stem cell differentiation was widely thought to be a developmentally default state, we have recently proposed that GSC lineage differentiation is controlled extrinsically by a differentiation niche formed by inner germarial sheath cells (ISCs, known as escort cells). It remains unclear how the maintenance and function of the differentiation niche are regulated at the molecular level. We show that autocrine Wnt2/4 signaling maintains the differentiation niche by regulating ISC proliferation and survival via redox regulation
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