Specification of Hematopoietic Stem Cell Identity

Adult stem cells maintain proliferating cellular systems for life. They do this by generating not only cells primed to enter differentiation pathways, but also cells that instead retain the undifferentiated stem cell characteristics of the parent.

Generation of new stem cells is called "self-renewal". We are interested in two aspects of self-renewal. The first concerns the genes that come into play when stem cells undergo self-renewal divisions. The second concerns the means by which some initially renewing daughter cells lose self-renewal capacity while others continue to retain it through multiple cell divisions. We use the hemopoietic system to model these processes. Our findings have led us to focus increasingly on particular homeobox genes as central effectors of self-renewal divisions, and on the genes that control their expression as specifiers of stable stem cell identity in this system.

A more detailed description can be found at our laboratory homepage: http://www.uhnres.utoronto.ca/iscovelab/

Graduate Student(s):

Postdoctoral Fellows (s):

• Catherine Frelin

Selected References:

For a more complete Pubmed listing of this researchers recent publications, click here. A selection is given below:

• Hematopoietic stem cells engraft in mice with absolute efficiency. P Benveniste, C Cantin, D Hyam, NN Iscove. Nature Immunology. 4:708-713, 2003.

• In vitro and in vivo expansion of hematopoietic stem cells. G Sauvageau, NN Iscove, RK Humphries. Oncogene. 23:7223-7232, 2004.

• Identification of gene 3' ends by automated EST cluster analysis. EM Muro, R Herrington, S Janmohamed, C Frelin, MA Andrade-Navarro, NN Iscove. Proc Natl Acad Sci USA. 105:20286-90, 2008.

• Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential. P Benveniste, C Frelin, S Janmohamed, M Barbara, R Herrington, D Hyam, NN Iscove. Cell Stem Cell. 6:48-58, 2010.