Adult stem cell niches for tissue homeostasis

Abstract

Adult stem cells are fundamental to maintain tissue homeostasis, growth, and regeneration. They reside in specialized environments called niches. Following activating signals, they proliferate and differentiate into functional cells that are able to preserve tissue physiology, either to guarantee normal turnover or to counteract tissue damage caused by injury or disease. Multiple interactions occur within the niche between stem cell-intrinsic factors, supporting cells, the extracellular matrix, and signaling pathways. Altogether, these interactions govern cell fate, preserving the stem cell pool, and regulating stem cell proliferation and differentiation. Based on their response to body needs, tissues can be largely classified into three main categories: tissues that even in normal conditions are characterized by an impressive turnover to replace rapidly exhausting cells (blood, epidermis, or intestinal epithelium); tissues that normally require only a basal cell replacement, though able to efficiently respond to increased tissue needs, injury, or disease (skeletal muscle); tissues that are equipped with less powerful stem cell niches, whose repairing ability is not able to overcome severe damage (heart or nervous tissue). The purpose of this review is to describe the main characteristics of stem cell niches in these different tissues, highlighting the various components influencing stem cell activity. Although much has been done, more work is needed to further increase our knowledge of niche interactions. This would be important not only to shed light on this fundamental chapter of human physiology but also to help the development of cell-based strategies for clinical therapeutic applications, especially when other approaches fail.

Keywords: bone marrow; central nervous system; heart; skeletal muscle; skin; stem cell niches; tissue homeostasis.

Figure 1

Schematic drawing of bone marrow niche summarizing its main components. Upon activation, long‐term hematopoietic stem cells (LT‐HSCs) divide asymmetrically, producing short‐term HSCs (ST‐HSCs) that give rise to multipotent progenitors that are able to ensure normal hematopoiesis for up to 3–4 months.

Figure 2

Schematic drawing of skin epidermal niches. Left: Interfollicular epidermis, the epidermal region located between hair follicles; basal stem cells continuously produce daughter cells, which moving upward (gray arrow), progressively differentiate into suprabasal layer cells. Right: During the hair cycle, primed bulge stem cells migrate along the outer root sheath of the hair shaft toward the dermal papilla within a cluster of cells called the matrix; here they proliferate and differentiate to produce the hair shaft and the inner root sheath

Figure 3

Schematic drawing of the crypt‐villus axis in the small intestine summarizing its main components. Left: The main types of epithelial cells are indicated in two adjacent villi. Right: Enlargement of the crypt bottom, containing intestinal stem cells (slow‐cycling B‐cell‐specific Moloney murine leukemia virus insertion site 1, Bmi1, and fast‐cycling leucine‐rich repeat‐containing G protein–coupled receptor 5 positive, Lgr5+). Lgr5+ divide producing transit‐amplifying (TA) cells that differentiate into the various absorptive and secretory cell types as they migrate toward the apex of the villus. Moving to the bottom of the crypt, some TA cells differentiate into Paneth cells. EE, enteroendocrine cell; TA, transit‐amplifying

Figure 4

Schematic drawing of a skeletal muscle niche. Satellite cells are small mononucleated cells located between the sarcolemma and the basal lamina. Satellite cells may undergo symmetric or asymmetric division. By symmetric division, two identical progenitor cells are produced, both equally in contact with the sarcolemma and the basal lamina. Otherwise, by asymmetric division, the daughter cell in contact with the basal lamina inherits the role of an uncommitted progenitor, whereas the other, adjacent to the sarcolemma, may undergo myogenic differentiation. Proliferating myoblasts are then produced and, after their fusion, new syncytial contractile muscle cells are assembled

Figure 5

Schematic drawing of neural niches and their main components. Top: Neural stem cell (NSC) niche in the subventricular zone of the lateral ventricle (SVZ); located underneath ependymal cells, NSCs produce transit‐amplifying (TA) progenitors that are able to differentiate into the three main nervous cell types: neurons, astrocytes, and oligodendrocytes. Bottom: Neural stem cells in the subgranular zone of the hippocampus (SGZ) reside at the interface between the hilus and the granule cell layer of the dentate gyrus; in this niche, NSCs give rise to neurons through intermediate precursors that migrate toward the granule cell layer and become mature neurons. CSF, cerebrospinal fluid