Totipotency, pluripotency and nuclear reprogramming

Abstract

Mammalian development commences with the totipotent zygote which is capable of developing into all the specialized cells that make up the adult animal. As development unfolds, cells of the early embryo proliferate and differentiate into the first two lineages, the pluripotent inner cell mass and the trophectoderm. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the nuclear reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient's own somatic cells can be used for reprogramming thereby eliminating immune based rejection of transplanted cells. In this review, we summarize two major approaches to reprogramming: (1) somatic cell nuclear transfer and (2) direct reprogramming using genetic manipulations.

Fig. 1

Development and reprogramming. Ontogeny begins from a single cell, the zygote. The zygote and each blastomere of the early embryo are totipotent with the potential to develop into the whole organism. As development unfolds, the developmental potential of individual blastomeres gradually declines resulting subsequently in pluripotent, multipotent, unipotent and terminally differentiated somatic cells. However, developmental potential of somatic cells can be reinstated to the totipotent stage by SCNT or to the pluripotent state by direct reprogramming

Fig. 2

A schematic diagram showing experimental steps in reprogramming of adult primate somatic cells into pluripotent embryonic stem cells via SCNT. A donor nucleus from a skin cell was introduced into an enucleated oocyte and the resulting embryo gave rise to embryonic stem cells (copied from [53], supplementary information)