This detailed information has helped researchers understand the origin of blood diseases and cancers and has led to advances in bone marrow transplantation. However, studies in mice can never substitute our understanding of hematopoiesis in humans.
Ravindra Majeti, MD, PhD, Instructor in hematology, Stanford University
The top hierarchy of human blood-forming system has not been investigated very well since 1988, when the Irving Weissman lab at Stanford University was only beginning to describe mouse hematopoetic stem cells (HSCs) and to establish the canonical scheme of mouse hematopoiesis based on immunotyping with surface markers.
Weissman basically divided HSCs into long-term (capable to self-renew and give long-term repopulation) and short-term (LT-HSC and ST-HSC). The next step in the differentiation tree from long-term HSCs is a group of multipotent progenitors (MPPs) which are capable to give the two main branches of hematopoiesis – lymphoid and myeloid.
Later on, a few research groups around the world have made some changes for “Weissman scheme”, based on differences in the expression of surface markers as detected by flow cytometry.
This scheme is show revised models of LSK (Lin–/Sca1+/C-kit+) HSCs hierarchy based on differential expression of surface markers (from Yang L, et al. Blood 2005;105;7:2717-2723 modified)
In the human hematopoesis hierarchy, long-term and short-term HSCs are yet to be characterized as well as MPP. Even the existence of these populations remain under question. In the recent study published by the Weissman group in the journal Cell Stem Cell, human MPPs are now characterized for the first time.
Authors of the study Ravinder Majeti and Christopher Park identified MPPs in human cord blood based on the expression of surface markers CD90 (Thy-1) and CD45RA on the surface in the previously described human HSCs (Lin-/CD34+/CD38-). The first news of this report is the precise identification of human long-term HSCs. Researchers showed long-term multipotent human hematopoiesis with transplantation as few as 10 Lin-/CD34+/CD38-/CD90+/CD45RA- cells in a xenogeneic model using NOG mice. Only this population contained two important properties of HSCs – multipotency and long-term self-renewal ability. Human MPPs were identified as Lin-/CD34+/CD38-/CD90-/CD45RA- population which were still multipotent but were not able to rescue long-term hematopoiesis and self-renewal.
So, up today “human scheme” of top hierarchy looks like this:
The characterization of the earliest stages of human hematopoiesis by the Weissman group advances our understanding of blood disorders. Because of the known difference in the CD90 expression between normal human HSCs (CD90+) and leukemia-initiating cells derived from acute myeloid leukemias (AML) in human (Blair A,1997), the study could also implies a new route for targeting leukemic stem cells (LSC).
Two interesting hypothesis came up in this paper:
1. AML LSC are indeed derived from HSCs but have aberrantly lost expression of CD90,
2. AML LSC do not derive from HSC but instead come from a downstream progenitor that lacks expression of CD90
Stanford University Medical Center (2007, December 13). Granddaddy Of Human Blood Cells Identified. ScienceDaily. Retrieved January 22, 2008, from http://www.sciencedaily.com/releases/2007/12/071212201951.htm