Blood stem cell fate regulation by Delta-1–mediated rewiring of IL-6 paracrine signaling

Author:

Csaszar Elizabeth12,Wang Weijia1,Usenko Tatiana1,Qiao Wenlian1,Delaney Colleen34,Bernstein Irwin D.34,Zandstra Peter W.12567

Affiliation:

1. Institute for Biomaterials and Biomedical Engineering and

2. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada;

3. Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA;

4. Seattle Children's Hospital, Seattle, WA;

5. Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada;

6. Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada; and

7. McEwen Centre for Regenerative Medicine, University Health Network, Toronto Medical Discovery Tower, Toronto, ON, Canada

Abstract

Key Points The Notch ligand Delta-1 reduces membrane bound IL-6R expression, inhibiting IL-6 cis-signaling and the production of myeloid cells. Combined with a dynamically fed culture system that minimizes IL-6 trans-signaling, Delta-1 produces rapid and sustained HSC engraftment.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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