Recent findings from the laboratory of Dr. John Dick shed new light on early cell fate determination in human hematopoiesis. Results, published online June 13, 2010 in Nature Immunology, demonstrate that the immature bone marrow precursors to B, T, and NK lymphocytes termed the multilymphoid progenitors (MLP), give rise to lymphoid and myeloid cells. Identification of this cell type disputes the “classic” model of hematopoiesis, which predicts that the segregation of lymphoid and myeloid lineages occurs very early in hematopoietic differentiation.

Seven distinct progenitor fractions were isolated from neonatal cord blood and adult bone marrow using flow cytometry to sort cells on the basis of a panel of seven markers. Using in vitro and in vivo assays, researchers identified that single MLP cells could give rise to all lymphoid cell types, including B cells, T cells, NK cells, dendritic cells and macrophages, but not granulocytes or erythrocytes. Gene expression analysis showed that the expression of lineage markers in these progenitors correlated with their functional potential, and indicated that MLP cells initiate the expression of lymphoid transcripts while maintaining a shared gene expression signature with myeloid progenitors.

Although myeloid commitment follows the classical model of hematopoiesis, where there is a loss of lymphoid potential at an early stage and subsequent segregation of myeloid and erythroid potential, identification of MLP cells demonstrates that the lymphoid and myeloid potential of immune cells separates in a gradual transition, rather than very early in hematopoietic differentiation. The identification of MLPs has important therapeutic advantages since they can be easily isolated, expanded and differentiated to obtain large quantities of T cells and dendritic cells, and may be a useful cell type for immunotherapy.

Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE. Nature Immunology. 2010 June 13. [Abstract]

The McEwen Centre, along with Cheryl and Robert McEwen and several McEwen investigators, was recently featured in the June Supplement of The Scientist, which highlights life sciences research in Ontario. “A Living Legacy” describes the discovery of the first stem cell in Toronto in the 1960’s by Till and McCulloch, and how stem cell and regenerative medicine research continues to flourish in the Toronto community. McEwen investigators highlighted in this article for their work include Drs. Gordon Keller, Andras Nagy, John Dick, Derek van der Kooy and Freda Miller. Andras Nagy is also featured in “Pluri-Pioneer” for his ground-breaking research using both embryonic and induced pluripotent stem cells, and an article written by Rob and Cheryl McEwen shares how their generous donation established the McEwen Centre, and the importance of private donations for accelerating the benefits of medical science.

The 8th Annual International Society for Stem Cell Research (ISSCR) Meeting is taking place June 16-19, 2010 in San Francisco, CA. More than 3,000 stem cell investigators will attend the “world’s premier stem cell research event”. This year’s sessions include a workshop titled “Stem Cell Therapies in Clinical Trials”, along with several Plenary and Concurrent sessions, including: ”Reprogramming and Pluripotency”, “Neural Stem Cells” and “Cardiac Stem Cells for Development and Regeneration”, which features a talk from Dr. Gordon Keller. Next year’s ISSCR Annual Meeting will take place from June 15-18, 2011 in Toronto.