Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells.
作者:
Tomokatsu(Ikawa),Masuda(Kyoko),Huijskens(Mirelle J A J),Satoh(Rumi),Kakugawa(Kiyokazu),Agata(Yasutoshi),Miyai(Tomohiro),Germeraad(Wilfred T V),Katsura(Yoshimoto),Kawamoto(Hiroshi)
状态:
发布时间2016-02-16
, 更新时间 2016-02-17
期刊:
Stem Cell Reports
摘要:
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.