Intrinsic and extrinsic control of the balance between stem cell self‐renewal and differentiation

Abstract

Stem cells in adult tissues have the capacity to self‐renew and generate differentiated progeny that replenish lost or damaged cells. Drosophila ovarian germline stem cells (GSCs) are an effective system for studying relationships between the niche and stem cells because of well defined stem cells and niche and availability of versatile genetic tools. Our previous studies have revealed how extrinsic niche signals and intrinsic factors to work together to control GSC self‐renewal. Niche cells use BMP signaling to control GSC self‐renewal by repressing differentiation, and E‐cadherin to anchor GSCs for long‐term self‐renewal. We have recently identified intrinsic factor Lis1 for its requirement for facilitating BMP signaling and E‐cadherin‐mediated cell adhesion and thereby GSC self‐renewal. In addition, we and others have shown that somatic escort cells are maintained by self‐duplication and play an important role in the regulation of germ cell differentiation. Recently, we have shown that H3K9 trimethylase Eggless is required in escort cells for controlling germ cell differentiation and in GSCs themselves for self‐renewal. Thus, the balance between stem cell self‐renewal and differentiation is controlled by concerted actions of extrinsic signals and intrinsic factors. Recently, we have applied this knowledge to convert adult fibroblasts into neural progenitor cells using a combination of lineage‐specific factors and growth factors.