1006 - Human Normal Haematopoetic Stem Cell Heterogeneity

Abstract

The haematopoietic system has long served as a model of choice for delineating mechanisms regulating self-renewal and differentiation. The majority of our understanding of the Haematopoietic Stem/Progenitor Cell (HSPC) compartment originated from mouse studies. Considerable efforts have been made in recent years in determining the composition of the cell types that constitute the mouse and human haematopoietic stem cell (HSC) compartment as well as the mechanisms that regulate the properties these cells. Using single cells transplantation assays with homogeneously highly purified mouse HSCs has been essential for the discovery of a new level of heterogeneity at the HSC level as well as describing alterations in HSC properties during ontogeny and aging. Our understanding of human HSC compartment compare to mouse HSCs is still in its infancy. Indeed, despite the clinical use of human HSC in transplantation more than fifty year ago, human HSCs have only been characterised relatively recently thanks to the development of the xenotransplantation assays and the refinement of immune- deficient mouse strains used. As in the mouse, purification of human HSCs requires the simultaneous detection of several independent cell surface markers. The discovery of CD34 antigen on human HSC and progenitors has transformed and accelerated studies on human hematopoietic development and is still commonly used to anticipate the adequacy of clinical haematopoietic cell transplants. Nevertheless, a few years ago, several groups including ours, have provided evidence of various types of human HSCs that do not express detectable levels of CD34. Our understanding of the biology of these CD34 negcells and the contribution of this rare population to the maintenance of human hematopoiesis remains limited. On the other hand, the CD34pos HSC fraction has been further refined thanks to the use of extra cell surface markers (CD90 and CD49f) (Notta et al., 2011) [1Notta F. Doulatov S. Laurenti E. et al.Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment.Science. 2011; 333: 218-221Crossref PubMed Scopus (603) Google Scholar]. We also more recently show that CD34neg HSCs define a unique human HSC subset differing from CD34 pos HSC not only phenotypically but also based on their engraftment kinetics, growth factors requirement and dormancy state (Anjos Afonso et al., 2013) [2Anjos-Afonso F. Currie E. Palmer H.G. et al.CD34(-) cells at the apex of the human hematopoietic stem cell hierarchy have distinctive cellular and molecular signatures.Cell Stem Cell. 2013; 13: 161-174Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar]. In this talk, we will review what is known about these two human HSC fractions, and discuss the potential clinical impacts. Keywords: Human HSC, Heterogeneity, Self-renewal, Dormancy.