Induced developmental arrest of early hematopoietic progenitors leads to the generation of leukocyte stem cells

Ikawa, Tomokatsu, Masuda, Kyoko, Huijskens, Mirelle J. A. J., Satoh, Rumi, Kakugawa, Kiyokazu, Agata, Yasutoshi, Miyai, Tomohiro, Germeraad, Wilfred T. V., Katsura, Yoshimoto, Kawamoto, Hiroshi

doi:10.1016/j.stemcr.2015.09.012

Self-renewal potential and multipotency are hallmarks of a stem cell. It is generally accepted that acquisition of such stemness requires rejuvenation of somatic cells through reprogramming of their genetic and epigenetic status. We show here that a simple block of cell differentiation is sufficient to induce and maintain stem cells. By overexpression of the transcriptional inhibitor ID3 in murine hematopoietic progenitor cells and cultivation under B cell induction conditions, the cells undergo developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost indefinitely, and the long-term cultured cells exhibit robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from human cord blood stem cells, and these will ultimately be useful as a source of cells for immune cell therapy.

Induced developmental arrest of early hematopoietic progenitors leads to the generation of leukocyte stem cells

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