“The manipulation of stem cell self-renewal is critically important for regenerative and transplantation medicine.”

Stem cells play crucial roles in transplantation and regenerative medicine. However, little is known about the mechanisms that control their self-renewal. We think that this self-renewal is a process whereby the cellular memory of stem cells, i.e., through which gene expression patterns of the mother stem cell is faithfully inherited by daughter cells. Our paper provides experimental evidence for the epigenetic regulation of stem cell self-renewal by the polycomb group protein, Bmi-1. This is a new and attractive concept in stem cell biology.

Polycomb proteins form a complex in order to exert their function. We show that, among them, Bmi-1 plays a central role in stem cells. Technically, our paper is based on the FACS (fluorescent activated cell sorting) isolation of highly purified hematopoietic stem cells and the highly efficient retroviral transduction of purified hematopoietic stem cells. By combining these techniques, we demonstrated a successful clonal analysis of the effect of Bmi-1 on hematopoietic stem cell self-renewal featuring paired-daughter cell experiments.

This paper is part of the key to understanding how a stem cell transfers its multipotential capacity to daughter cells during cell division and also provides a clue to the manipulation of stem cells for regenerative medicine.

For us, the hematopoietic system is a good model for the study of stem cell biology. We have screened molecules that enhance hematopoietic stem cell self-renewal. Recent advances in epigenetic regulation of cellular memory prompted us to try polycomb genes, and we found out what Bmi-1 actually does.

The manipulation of stem cell self-renewal is critically important for regenerative and transplantation medicine. The epigenetic regulation of stem cell self-renewal by Bmi-1 has also been reported in the neuronal stem cell system. If this is indeed the common mechanism among different stem cells, Bmi-1 could be a good molecular target in order to manipulate stem cell self-renewal. We are currently examining this possibility by analyzing both somatic and germline stem cells.