EXPRESSION OF GROWTH-FACTORS DURING THE DIFFERENTIATION OF EMBRYONIC STEM-CELLS IN MONOLAYER

Embryonic stem (ES) cells, derived in culture directly from the inner cells mass (ICM) of blastocysts, more closely resemble their embryonic counterparts than the more commonly used embryonal carcinoma (EC) cells derived from teratocarcinomas. In view of the potential role of growth factors in early development, we have now followed changes in the expression of transforming growth factor β (in particular TGFβ1, β3, β4), platelet-derived growth factor (PDGF-A, PDGF-B) and insulin-like growth factor (IGF II) during the differentiation of ES cells in monolayer. When maintained in medium conditioned by Buffalo rat liver cells (BRL-CM) to inhibit differentiation, ES cells expressed 2.5 and 1.8 kb transcripts for TGFβ1, as well as transcripts for TGFβ4, PDGF-A, and low levels of PDGF-B, but not TGFβ3 or IGF II. After formation of parietal endoderm-like cells by addition of retinoic acid (RA) to BRL-CM, the 1.8-kb transcript of TGFβ1 and PDGF-A expression were reduced, IGF II mRNA and a single TGFβ3 transcript of 3.8 kb were induced while PDGF-B and TGFβ4 remained virtually unchanged. By contrast, in ES cells induced to differentiate by the absence of BRL-CM, unusual transcripts for TGFβ3 of 3.0 and 6.0 kb became detectable and PDGF-B expression increased. The changes in growth factor expression in ES cells are compared with those in F9 and P19 EC cells induced to differentiate in monolayer by RA. © 1990 Academic Press, Inc.