originally cloned and characterized c- mpl as the human homolog of the v- mpl oncogene from the cDNA library of the human erythroid leukemia cell line. TPO interacts with the surface receptor, c-mpl, a member of the hematopoietic growth factor receptor superfamily.

The question remained whether TPO was affecting a broad array of lineage-committed progenitor cells, or alternatively, acting on earlier multipotent progenitors and primitive pluripotent stem cells. However, evidence has accumulated to indicate that TPO also exerts significant influence on other hematopoietic lineages as well. Thrombopoietin (TPO) is a cytokine isolated by several groups and determined to be the primary regulator of lineage-committed megakaryocyte and platelet development. Many studies of HSC have identified factors that influence maintenance or self-renewal of the stem cell and factors that lead to differentiation and lineage commitment. Subsequent studies have confirmed the basic tenets of this model, and shown that the CD34 +CD38 - stage I HSC/PC are highly enriched for pluripotent stem cell activity, including long-term culture-initiating cells (LTC-IC) and long-term repopulating stem cells. Stages I (CD34 ++CD38 -) and II (CD34 ++/+CD38 +/++) included the uncommitted, multipotent progenitor cells stages III (CD34 +CD38 +++) and IV (CD34 dimCD38 +++) included the lineage-committed progenitor cells. Based on the differential expression of the CD34 and CD38 differentiation antigens, the lineage-associated antigens CD71, CD33, CD10, CD5 and CD7, together with forward and orthogonal light-scattering properties, the authors developed a model for human ABM HSC/PC differentiation to include four progressive developmental stages I through IV. found that expression of CD38 is an early event in the differentiation of human CD34 + adult bone marrow (ABM) cells into the erythroid, myeloid and lymphoid lineages, and therefore, a useful marker for indicating early lineage commitment. CD38 is a 45 kD glycoprotein whose function is unknown. The CD38 antigen has been useful to further identify CD34 + HSC/PC that have begun the initial stages of lineage commitment. In order to more finely delineate those CD34 Bright cells which possess the reconstitutive and self-renewal properties of primitive HSC, other cell surface antigens have been investigated, such as CD38, CD50, HLA-DR, CD71, CD90, CD117, and more recently CD133 and CDCP1. The long-term multipotent repopulating capability of CD34 + HSC/PC, which encompasses B- and T-lymphoid, myelomonocytic, erythroid, and megakaryocytic reconstitution in vivo, resides within the CD34 Bright fraction. Human hematopoietic cells expressing the CD34 antigen are enriched for HSC/PC, but represent a heterogeneous population, including early progenitors with high levels of CD34 (CD34 Bright), and lineage-committed progenitors, with decreasing levels of CD34 as they differentiate (CD34 dim).

Historically, the surface marker most commonly used for human HSC/PC isolation has been the CD34 antigen.

It is now common practice to utilize monoclonal antibodies raised against an array of relevant cell surface antigens for the identification and purification of subpopulations of human hematopoietic stem/progenitor cells (HSC/PC). Positive selection strategies allow transplantation of HSC capable of long-term multilineage hematopoietic reconstitution, while avoiding transfer of cells responsible for graft versus host disease in the allogeneic setting, or contaminating tumor cells in the autologous setting.

Isolation of candidate human HSC allow investigations into stem cell renewal, expansion, and key events in lineage commitment during maturation and development. Practical and accurate identification of primitive human HSC is useful for both research investigation of stem cell physiology, as well as for clinical applications, such as stem cell transplantation, stem cell expansion and gene therapy. Elucidating the nature and biology of the primitive pluripotent hematopoietic stem cell (HSC) has been a major goal of research efforts in hematopoiesis.

Scid vs.pc