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Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
bioRxiv - Developmental Biology Pub Date : 2020-05-25 , DOI: 10.1101/2020.05.22.107045
John Parkin Russell , Xinhong Lim , Alice Santambrogio , Val Yianni , Yasmine Kemkem , Bruce Wang , Matthew Fish , Scott Haston , Anaëlle Grabek , Shirleen Hallang , Emily Jane Lodge , Amanda Louise Patist , Andreas Schedl , Patrice Mollard , Roeland Nusse , Cynthia Lilian Andoniadou

In response to physiological demand, the pituitary gland generates new hormone-secreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+ stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+ PSCs in vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+ PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells.

中文翻译:

垂体干细胞产生旁分泌WNT信号,以控制其后代祖细胞的扩增

响应生理需求,垂体在整个生命过程中从定型祖细胞中产生新的激素分泌细胞。尚不清楚在何种程度上专门表达SOX2的垂体干细胞(PSC)促进垂体的生长和更新。此外,尚未阐明驱动增殖的信号或其来源。我们在小鼠中使用了遗传学方法,表明WNT途径对于腺体所有谱系的增殖至关重要。我们揭示SOX2 +干细胞是WNT配体的关键来源。通过阻止体内SOX2 + PSC分泌WNT,我们证明邻近的定殖祖细胞的增殖下降,表明祖细胞增殖取决于SOX2 + PSC分泌的旁分泌WNT。
更新日期:2020-05-25
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