The blood system is organized as a developmental hierarchy in which rare hematopoietic stem cells (HSCs) generate large numbers of immature progenitors and differentiated mature blood cells. In this process, at least ten distict lineages are specified from multipotent stem cells, however the cellular and molecular organization of the hematopoietic hierarchy is a topic of intense investigation. While much has been learned from mouse models, there is also an appreciation for species-specific differences and the need for human studies. Blood lineages have been traditionally grouped into myeloid and lymphoid branches, and the long-standing dogma has been that the separation between these branches is the earliest event in fate specification. However, recent murine studies indicate that the progeny of initial specification retain the more ancestral myeloid potential. By contrast, much less is known about the progenitor hierarchy in human hematopoiesis. To dissect human hematopoiesis, we developed a novel sorting scheme to isolate human stem and progenitor cells from neonatal cord blood and adult bone marrow. As few as one in five single sorted HSCs efficiently repopulated immunodeficient mice enabling interrogation of homogeneous human stem cells. By analyzing the developmental potential of sorted progenitors at a single-cell level we showed that earliest human lymphoid progenitors (termed LMPs) possess myelo-monocytic potential. In addition to B-, T-, and natural killer cells, LMPs gave rise to dendritic cells and macrophages indicating that these closely related myeloid lineages also remain entangled in lymphoid development. These studies provide systematic insight into the organization of the human hematopoietic hierarchy, which provides the basis for detailed genetic analysis of molecular regulation in defined cell populations. In a pilot study, we investigated the role of a zinc finger transcription factor (ZNF145), PLZF, in myeloid development. We found that PLZF restrained proliferation and differentiation of myeloid progenitors and maintained the progenitor pool. Induction of ERK1/2 by myeloid cytokines, reflective of a stress response, leads to nuclear export and inactivation of PLZF, which augments mature cell production. Thus, negative regulators of differentiation can serve to maintain developmental systems in a primed state, so that their inactivation by extrinsic signals can induce proliferation and differentiation to rapidly satisfy increased demand for mature cells. Taken together, these studies advance our understanding of the cellular and molecular architecture of human hematopoiesis.

Hematopoietic stem/progenitor cells (HSPC) play main role in constituting the whole hematopoietic system. Furthermore, since recognized in 1960s, HSPC are utilized to protect patients from severe chemo and radio therapy. As time goes, they are also used to treat hematopoietic disorders such as leukemia. Bone marrow, peripheral blood and umbilical cord blood are now the three sources of HSPC. Umbilical cord blood seems optimal because it is easy to obtain, no risk to graft donor and low probability of infection transmission. However, low number of HSPCs in umbilical cord blood is the main limitation. My research focuses mainly on in-vitro proliferation of HSPCs. In addition, I also worked on labeling HSPC in-vitro for tracking these cells after transplantation. The experimental results indicated that HSPCs are effectively labeled and their proliferation rate is significantly enhanced in-vitro. / N/A

Thesis (PhD in AppSc)--University of South Australia, 1996

Bibliography: leaves 152-223. / xxiii, 223, [137] leaves, [27] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Experiments were designed to identify and purify human bone marrow stromal precursor cells by positive immunoselection, based on the cell surface expression of the VCAM-1 and STRO-1 antigens. The data presented demonstrates a hierarchy of bone cell development in vitro. / Thesis (Ph.D.)--University of Adelaide, Dept. of Orthopaedics Surgery and Trauma, 1998

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Orthopaedics Surgery and Trauma, 1998. / Bibliography: leaves 152-223.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 151-192) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 151-192) Also available online.

Thesis (M.S.)--Brandeis University, 2009. / Title from PDF title page (viewed on May 29, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Nevada, Reno, 2005. / Includes bibliographical references. Online version available on the World Wide Web.