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Biomedical subjects

Jean C Y Wang

Publications and source records attributed to Jean C Y Wang.

3 recordsLinked to original sources

Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment.

Hematopoiesis requires tight regulation of the hematopoietic stem cell (HSC) population; however, the dynamics of HSC use at steady state are uncertain. Over 3-7 months, we evaluated the repopulation and self-renewal of more than 600 individual human 'severe combined immunodeficiency mouse-repopulating cells' (SRCs), tracked on the basis of lentiviral integration sites, in serially transplanted immune-deficient mice, as well as of SRC daughter cells that migrated to different marrow locations in a single mouse. Our data demonstrate maintenance by self-renewing SRCs after an initial period of clonal instability, a result inconsistent with the clonal succession model. We found wide variation in proliferation kinetics and self-renewal among SRCs, as well as between SRC daughter cells that repopulated equivalently, suggesting that SRC fate is unpredictable before SRCs enter more rigid 'downstream' developmental programs.

ADP-ribosyl Cyclase 1↗

Cancer stem cells: lessons from leukemia.

A fundamental problem in cancer research is identification of the cell type capable of initiating and sustaining growth of the tumor--the cancer stem cell (CSC). While the existence of CSCs was first proposed over 40 years ago, only in the past decade have these cells been identified and characterized in hematological malignancies. Recent studies have now described CSCs in solid tumors of the breast and brain, raising the possibility that such cells are at the apex of all neoplastic systems. An appreciation of the biological distinctness of CSCs is crucial not only for the design of studies to understand how tumorigenic pathways operate but also for the development of specific therapies that effectively target these cells in patients.

Animals↗

Concepts of human leukemic development.

Two fundamental problems in cancer research are identification of the normal cell within which cancer initiates and identification of the cell type capable of sustaining the growth of the neoplastic clone. There is overwhelming evidence that virtually all cancers are clonal and represent the progeny of a single cell. What is less clear for most cancers is which cells within the tumor clone possess tumorigenic or 'cancer stem cell' (CSC) properties and are capable of maintaining tumor growth. The concept that only a subpopulation of rare CSC is responsible for maintenance of the neoplasm emerged nearly 50 years ago. Testing of this hypothesis is most advanced for the hematopoietic system due to the establishment of functional in vitro and in vivo assays for stem and progenitor cells at all stages of development. This body of work led to conclusive proof for CSC with the identification and purification of leukemic stem cells capable of repopulating NOD/SCID mice. This review will focus on the historical development of the CSC hypothesis, the mechanisms necessary to subvert normal developmental programs, and the identification of the cell in which these leukemogenic events first occur.

Acute Disease↗