Keeping stem cells under control: New insights into the mechanisms that limit niche‐stem cell signaling within the reproductive system

Abstract

Summary Adult stem cells reside in specialized microenvironments called niches that maintain stem cells in an undifferentiated and self-renewing state. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, the mechanisms that restrict niche signal exclusively to stem cells remained elusive: such a mechanism is crucially important to ensure that stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, differentiate. Here, we review recent progress on the characterization of niche-stem cell interactions with special focus on emerging mechanisms that spatially restrict niche signaling. Adult stem cells reside in specialized microenvironments called niches that maintain stem cells in an undifferentiated and self-renewing state. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, the mechanisms that restrict niche signal exclusively to stem cells remained elusive: such a mechanism is crucially important to ensure that stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, differentiate. Here, we review recent progress on the characterization of niche-stem cell interactions with special focus on emerging mechanisms that spatially restrict niche signaling.

Ectopic Germ Cells Can Induce Niche-like Enwrapment by Neighboring Body Wall Muscle

“…Niche enwrapment of stem cells and their differentiating progeny is a common, yet poorly understood, aspect of diverse niches that is thought to create a tightly regulated signaling, adhesive, and protective environment [10,11,14,15]. During zebrafish development, circulating hematopoietic stem and progenitor cells (HSPCs) trigger endothelial cell remodeling in the caudal hematopoietic tissue to form a pocket that constitutes the perivascular niche [10].…”

“…A common feature of niches in mice, zebrafish, and Drosophila is the cellular enwrapment of stem cells and their progeny by support cells [7,8,10,15,35,36]. We hypothesized that the cell surface proteins that control enwrapping behavior were commonly expressed in both the niche and muscle, thereby priming the muscle to respond to the presence of germ cells.…”

“…Cells that are enwrapped by supportive niche cells include mouse spermatogonial stem cells and their differentiating progeny [7]; Drosophila intestinal progenitor cells [8], primordial germ cells, germ stem cells, and their progeny [9]; zebrafish hematopoietic stem and progenitor cells [10]; and C. elegans germ cell progenitors [11], stem cells [12][13][14], and their progeny [12]. Niche enwrapment may increase surface area to either amplify or spatially restrict niche signaling, to physically anchor cells in the niche, and to create physiologically buffered microenvironments that nurture and protect stem cells [10,[13][14][15]. Understanding the mechanisms that regulate the establishment of physiological and ectopic niches has important implications for fertility, renewal of aged and damaged tissues, and the generation of tumor cell niches that sustain metastasis.…”

Identification of regulators of germ stem cell enwrapment by its niche in C. elegans

“…Niche cues are often restricted to stem cells in direct contact with niche cells (Inaba et al, 2016). In many niches, support cells extend cellular processes that enwrap stem cells.…”

Modulation of Cell–Cell Interactions in Drosophila Oocyte Development

“…Niche signals are thought to be "short-range" in nature, as these molecules influence the stem cell, but not nearby differentiating daughter cells. Specialized cellular protrusions have been reported to play essential roles in this process [22].…”