Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells.

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_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Ikawa T,Masuda K,Huijskens MJAJ,Satoh R,Kakugawa K,Agata Y,Miyai T,Germeraad WTV,Katsura Y,Kawamoto H

doi

10.1016/j.stemcr.2015.09.012

subject

Has Abstract

pub_date

2015-11-10 00:00:00

pages

716-727

issue

5

issn

2213-6711

pii

S2213-6711(15)00274-X

journal_volume

5

pub_type

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