Department of Genetics, Cell Biology and Development, The University of Minnesota, Minneapolis, Minnesota 55455.
Department of Genetics, Cell Biology and Development, The University of Minnesota, Minneapolis, Minnesota 55455
Genetics. 2018 Jun;209(2):537-549. doi: 10.1534/genetics.118.300839. Epub 2018 Apr 9.
Adult stem cells reside in specialized microenvironments called niches, which provide signals for stem cells to maintain their undifferentiated and self-renewing state. To maintain stem cell quality, several types of stem cells are known to be regularly replaced by progenitor cells through niche competition. However, the cellular and molecular bases for stem cell competition for niche occupancy are largely unknown. Here, we show that two members of the glypican family of heparan sulfate proteoglycans (HSPGs), Dally and Dally-like (Dlp), differentially regulate follicle stem cell (FSC) maintenance and competitiveness for niche occupancy. Lineage analyses of glypican mutant FSC clones showed that is essential for normal FSC maintenance. In contrast, is a hypercompetitive mutation: mutant FSC progenitors often eventually occupy the entire epithelial sheet. RNA interference knockdown experiments showed that Dally and Dlp play both partially redundant and distinct roles in regulating Jak/Stat, Wg, and Hh signaling in FSCs. The FSC system offers a powerful genetic model to study the mechanisms by which HSPGs exert specific functions in stem cell replacement and competition.
成体干细胞驻留在称为龛的专门微环境中，龛为干细胞提供维持其未分化和自我更新状态的信号。为了维持干细胞质量，已知几种类型的干细胞通过龛竞争被祖细胞定期替换。然而，干细胞竞争龛占据的细胞和分子基础在很大程度上是未知的。在这里，我们表明硫酸乙酰肝素蛋白聚糖 (HSPG) 家族的两个成员，Dally 和 Dally-like (Dlp)，差异调节滤泡干细胞 (FSC) 的维持和龛占据的竞争力。糖蛋白突变 FSC 克隆的谱系分析表明， 对于正常的 FSC 维持是必需的。相比之下， 是一个超竞争突变： 突变 FSC 祖细胞通常最终占据整个上皮层。RNA 干扰敲低实验表明，Dally 和 Dlp 在调节 FSCs 中的 Jak/Stat、Wg 和 Hh 信号通路方面发挥着部分冗余和不同的作用。FSC 系统提供了一个强大的遗传模型，用于研究 HSPG 在干细胞替换和竞争中发挥特定功能的机制。
