Journal Article 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

5 ( 5 )  , pp.716 - 727 , 2015-10-10 , Elsevier Inc.
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.

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