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

Abstract

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.

Journal

• Stem Cell Reports

  Stem Cell Reports 5 (5), 716-727, 2015-10-10

  Elsevier Inc.

Details

• CRID: 1050001335830006656
• NII Article ID: 120005745636
• ISSN: 22136711
• HANDLE: 2433/210242
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles