Advancing insights into stem cell niche complexities with next-generation technologies.

Adult tissue-specific stem cells are essential for homeostatic tissue maintenance and key to regeneration during injury repair or disease. Many critical stem cell functions rely on the presence of well-timed cues from the microenvironment or niche, which includes a diverse range of components, including neuronal, circulating and extracellular matrix inputs as well as an array of neighboring niche cells directly interacting with the stem cells. However, studies of stem cells and their niche have been challenging due to the complexity of adult stem cell functions, their intrinsic controls and the multiple regulatory niche components. Here, we review recent major advances in our understanding of the complex interplay between stem cells and their niche that were enabled by the tremendous technological leaps in single-cell transcriptome analyses, 3D in vitro cultures and 4D in vivo microscopy of stem cell niches.