Send to

Choose Destination
Nat Methods. 2017 May;14(5):531-538. doi: 10.1038/nmeth.4258. Epub 2017 Apr 10.

Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1.

Author information

Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Department of Immunology, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Medicine by Design, a Canada First Research Excellence Program at the University of Toronto, Toronto, Ontario, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.


The molecular and cellular signals that guide T-cell development from hematopoietic stem and progenitor cells (HSPCs) remain poorly understood. The thymic microenvironment integrates multiple niche molecules to potentiate T-cell development in vivo. Recapitulating these signals in vitro in a stromal cell-free system has been challenging and limits T-cell generation technologies. Here, we describe a fully defined engineered in vitro niche capable of guiding T-lineage development from HSPCs. Synergistic interactions between Notch ligand Delta-like 4 and vascular cell adhesion molecule 1 (VCAM-1) were leveraged to enhance Notch signaling and progenitor T-cell differentiation rates. The engineered thymus-like niche enables in vitro production of mouse Sca-1+cKit+ and human CD34+ HSPC-derived CD7+ progenitor T-cells capable of in vivo thymus colonization and maturation into cytokine-producing CD3+ T-cells. This engineered thymic-like niche provides a platform for in vitro analysis of human T-cell development as well as clinical-scale cell production for future development of immunotherapeutic applications.

Comment in

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center