Expression of liver fatty acid binding protein alters growth and differentiation of embryonic stem cells

Although expression of liver fatty acid binding protein (L-FABP) modulates cell growth, it is not known if L-FABP also alters cell morphology and diff erentiation. Therefore, pluripotent embryonic stem cells were transfected w ith cDNA encoding L-FABP and a series of clones expressing increasing level s of L-FABP were isolated. Untransfected ES cells, as well as ES cells tran sfected only with empty vector, spontaneously differentiated from rounded a dipocyte-like to fibroblast-like morphology, concomitant with marked reduct ion in expression of stage-specific embryonic antigen (SSEA-1). These chang es in morphology and expression of SSEA-1 were greatest in ES cell clones e xpressing L-FABP above a threshold level. Immunofluorescence confocal micro scopy revealed that L-FABP was primarily localized in a diffuse-cytosolic p attern along with a lesser degree of punctate L-FABP expression in the nucl eus. Nuclear localization of L-FABP was preferentially increased in clones expressing higher levels of L-FABP. In summary, L-FABP expression altered E S cell morphology and expression of SSEA-1. Taken together with the fact th at L-FABP was detected in the nucleus, these data suggested that L-FABP may play a more direct, heretofore unknown, role in regulating ES cell differe ntiation by acting in the nucleus as well as cytoplasm.