For the first time since stem cells were discovered here 50 years ago, scientists have isolated a human blood stem cell in its purest form – as a single stem cell capable of regenerating the entire blood system. This breakthrough opens the door to harnessing the power of these life-producing cells to treat cancer and other debilitating diseases more effectively. The study is published today in Science.
Science 8 July 2011:
Vol. 333 no. 6039 pp. 218-221
DOI: 10.1126/science.1201219
REPORT
Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment
Faiyaz Notta1,2,*, Sergei Doulatov1,2,*, Elisa Laurenti1,2, Armando Poeppl1, Igor Jurisica3,4, John E. Dick1,2,†
+ Author Affiliations
1Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, Ontario, Canada.
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
3Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.
4Departments of Computer Science and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
↵†To whom correspondence should be addressed. Toronto Medical Discovery Tower, Room 8-301, 101 College Street, Toronto, Canada M5G 1L7. E-mail: jdick@uhnres.utoronto.ca
↵* These authors contributed equally to this work.
ABSTRACT
Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f+ cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell–based therapeutics.
