Maintenance of pluripotential embryonic stem cells by stem cell selection

Abstract

As gastrulation proceeds, pluripotential stem cells with the capacity tocontribute to all primary germ layers disappear from the mammalian embryo. Theextinction of pluripotency also occurs during the formation of embryoid bodiesfrom embryonic stem (ES) cells. In this report we show that if the initialdifferentiated progeny are removed from ES cell aggregates, furtherdifferentiation does not proceed and the stem cell population persists andexpands. Significantly, the presence of even minor populations ofdifferentiated cells lead to the complete loss of stem cells from thecultures. This finding implies that the normal elimination of pluripotentcells is dictated by inductive signals provided by differentiated progeny. Wehave exploited this observation to develop a strategy for the isolation ofpluripotential cells. This approach, termed stem cell selection, may havewidespread applicability to the derivation and propagation of stem cells.