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Hydra anatomy and cycling properties of Hydra stem cells. (a) The Hydra polyp exhibits a radial symmetry centered on an oral–aboral axis. At the apical pole also called the head, a ring of tentacles surrounds a dome called hypostome that is centered on the mouth opening, while at the basal end called foot, the basal disc that produces mucus allows the animal to attach to substrates. The animal consists of two epithelial layers, the epidermis on the outside consisting of epidermal epithelial stem cells (eESCs), and the gastrodermis on the inside consisting of gastrodermal epithelial stem cells (gESCs). All epithelial cells along the gastric region are ESCs that terminally differentiate when they reach the extremities. Interstitial stem cells (ISCs) are abundant in the central region of the animal, interspersed with eESCs. (b) The cell cycle of ESCs lasts 3–4 days, while multipotent ISC cycle every 24–30 h. In each cycle, ISCs provide asymmetrically divided interstitial progenitors (IPs) that cycle faster than ISCs (less than 24 h). IPs are migratory cells that differentiate in G0 phase along the body axis and at the extremities. As for somatic derivatives, nematocytes are strictly located in the epidermis, nerve cells are found in both layers, and gland cells in the gastrodermis. Fast cycling cells such as ISCs and IPs are predominantly killed by hydroxyurea (HU) pulse treatment. In contrast, ESCs paused in G2 are resistant to such treatments. Passively moving toward the apical and basal poles, ESCs differentiate in G2 phase into head- and foot-specific epithelial cells. Scheme adapted after [6]