Normal and pathological development of pluripotent stem cells.

Abstract

Pluripotent cells of the early embryo originate all types of somatic cells and germ cells of adult organism. Pluripotent stem cell lines were derived from mammalian embryos and adult tissues using different techniques and from different sources--inner cell mass of the blastocyst, primordial germ cells, parthenogenetic oocytes, and mature spermatogonia--as well as by transgenic modification of various adult somatic cells. Despite different origin, all pluripotent stem cell lines demonstrate considerable similarity of the major biological properties: unlimited self-renewal and differentiation into various somatic and germ cells in vitro and in vivo, similar gene expression profiles, and similar cell cycle structure. Their malignant counterpart embryonal teratocarcinoma stem cell lines have restricted developmental potentials caused by genetic disturbances that result in deregulation of proliferation and differentiation balance. Numerous studies on the stability of different pluripotent stem cell lines demonstrated that, irrespective of their origin, long-term in vitro cultivation leads to the accumulation of chromosomal and gene mutations as well as epigenetic changes that can cause oncogenic transformation of cells. Our research of signaling pathways and pattern of specific gene expression in pluripotent stem cells and teratocarcinoma cells is focused on discovery of fundamental mechanisms that regulate normal development of pluripotent cells into different lineages and are disrupted in cancer initiating cells. Analysis gene expression profiles, differentiation potentials and cell cycle of normal and mutant pluripotent stem cells provide new data to search molecular targets to eliminate malignant cells in tumors.