Figure 2. SC dynamics across lineages.

(A) Squamous epithelia consist of layers of keratinocytes, SCs (green) reside in the basal cell layer, along with post-mitotic cells waiting to stratify (red). When a differentiating cell leaves the niche (arrow), a nearby SC divides with one of the three division outcomes shown to maintain constant cell density in the niche. The probabilities of each outcome (expressed as per cent, oesophageal epithelium shown) are balanced, so equal numbers of SCs and differentiated cells are produced across the population. (B) The hair follicle cycles between a resting stage (telogen) and expansion of the lower follicle (anagen). Multiple SCs have been identified, in the junctional zone (purple), the bulge (green) and the hair germ (blue), which lie in contact with the mesenchymal cells of the dermal papilla (blue). The hair shaft (black) is surrounded by concentric layers of inner root sheath cells that have been omitted for clarity. In the transition into anagen, hair germ and upper bulge cells self-duplicate. In the bulge, divisions are aligned parallel with the axis of the hair shaft (inset). Lower bulge cells contribute differentiating progeny to greatly expand the root sheath. Later in anagen, hair germ cells assemble around the dermal papilla and then generate inner root sheath cells (arrows). Self-renewal and differentiation are balanced, so the numbers of SCs in each compartment is maintained at a constant level across multiple hair cycles. (C) Intestinal epithelium contains four lineages sustained by SCs (green) that lie between Paneth cells in the crypt base. Differentiating cells migrate through a progenitor compartment in the upper crypt from which post-mitotic cells populate the villus, from which they are shed. Inset shows a simplified top-down view of the niche. As a differentiating SC exits the niche, it is replaced by the self-duplicating division of an immediately adjacent SC. (D) Heamatopoietic SCs reside close to blood vessels in the bone marrow. Dormant SCs (green) lie close to arterioles, receiving paracrine signals from endothelial cells (red), perivascular cells expressing Ng2 and sympathetic nerve endings (blue). On activation, SCs migrate to be close to venous sinusoids that support Lepr-expressing perivascular cells. (E) Asymmetric fate and symmetric fate of haematopoietic SCs. Transplantation of daughter cells of a single SC reveals self-duplicating and asymmetric divisions: dark green: long-term-reconstituting SCs; light green: short- or intermediate-term-reconstituting SCs; yellow: megakaryocyte progenitor; and blue: common myeloid progenitor. (F) Native haematopoiesis. Lineage tracing in homoeostasis suggests that myeloid lineages may be maintained by self-sustaining progenitor cells (yellow) exhibiting ‘population asymmetry’ by generating equal proportions of progenitor and differentiating cells (grey) (see inset). Haematopoietic SCs (green) make negligible contribution to myelopoiesis in homoeostasis, but function as ‘reserve’ cells. (G) Male germ cell SCs are diverse in appearance but functionally equivalent. Male germ cells expressing GFRα1 reside in the outermost layer of the seminiferous tubule. SCs (green) exist as singles or 2–4 cell syncytia connected by cytoplasmic bridges, which may self-duplicate (blue arrows) to generate two SCs or undergo fragmentation (short red arrows). Upon differentiation (pink arrow) into Ngn3-positive cells (red), the same behaviour continues, but Ngn3⁺ cells are unlikely to revert to GFRα1⁺ SCs in homoeostasis. Once in the Ngn3 compartment, syncytia larger than 4 cells form which may undergo further differentiation into cKit-expressing cells (not shown), which are even less likely to revert to GFRα1-positive cells. (H) Neural SCs exhibit symmetric and asymmetric cell divisions. Quiescent neural SCs (light green) reside in the subventricular zone niche, extending processes into cerebrospinal fluid (blue) that fills the lateral ventricles (LV) and underlying endothelial cells (red) lining blood vessels (BV). Endothelial cells that line the LV are shown in grey. Differentiating transit amplifying cells (pink) and neural precursor cells (orange) lie adjacent to the SCs. Figure after Silva-Vargas et al (2013). (I) Division outcomes of neural SCs in the dentate gyrus inferred from lineage tracing. Neural SCs interconvert between quiescent (light green) and proliferating (dark green) states. Division of SCs has a range of symmetric and asymmetric outcomes as shown, generating neural SCs, neuroblasts (orange) or differentiated astrocytes (blue).