Fig. 3.

Concepts in stem cell lineage organization. a “Differentiation on demand”: signals from differentiated cells instruct the fate choice of a pluripotent progenitor. b Stochastic differentiation. Purely cell-intrinsic mechanisms determine the fate choice of a pluripotent progenitor. Tissue loss due to injury (red line symbolizing amputation plane) could affect fate choices in a, but not in b. c Hypothetical differentiation hierarchy utilizing a combination of mechanisms. Initial lineage segregation occurs via cell intrinsic mechanisms (top). Terminal cell fates arise from additional choice points within lineages, involving a combination of (1) local “differentiation on demand” signals in the tissue environment (bottom left); (2) global patterning signals (centre) and (3) self-assembly of complex structures by means of spatiotemporal interactions amongst progenitors. Note that the scheme does not distinguish neoblasts and postmitotic progeny: initial lineage segregation (top) amongst postmitotic progeny would imply uniform neoblast pluripotency; lineage segregation already within dividing cells would imply neoblast heterogeneity in form of transit amplifying cells