20 TGF-β Family Signaling in Stem Cell Renewal and Differentiation

Stem cells are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation. Embryonic stem (ES) cells self-renew indefinitely and give rise to derivatives of all three primary germ layers. Somatic stem cells have also been identified in various adult organs, and in most cases, they exhibit limited abilities for self-renewal and differentiation. The capacity of ES cells and somatic stem cells for multilineage differentiation may yield replacement cell therapies for genetic, malignant, and degenerative diseases. The signaling cascades that govern stem cell renewal and differentiation have been the subject of extensive studies. The first half of this chapter describes how transforming growth factor-β (TGF-β) family signaling, in cooperation with other signaling cascades, maintains the self-renewal and pluripotency of human and mouse ES cells and induces their differentiation toward specific cell lineages. The second half of this chapter discusses the roles of TGF-β family signaling in the self-renewal and differentiation of somatic stem cells. TGF-β FAMILY SIGNALING IN ES CELLS Establishment of Mouse and Human ES Cells and Their Unique Features During early mouse embryogenesis, embryos are partitioned into extraembryonic and embryonic components. The embryonic component, referred to as the inner cell mass, is the source of all tissues of the developing embryo and fetus, and ultimately the adult organism. The inner cell mass also serves as the source of mouse ES cells. One of the defining features of mouse ES cells is their potential to undergo...