Biology Graduate Student Invited Speaker Seminar Series
Lineage reprogramming and stem cell-based therapies
By
Rita C. R. Perlingeiro
PC426 from 10 A.M -11 A.M on March 5th 2009
Summary: A major goal in my laboratory is to understand the events involved in lineage determination as pluripotent cells commit to mesodermal progenitors, in particular hematopoietic, endothelial, and myogenic cell fates. This knowledge is fundamental to the development of stem cell-based therapies.
Embryonic stem (ES) cells are endowed with self-renewal and broad differentiation potential. However, the generation of a population of myogenic progenitors from differentiating ES cells with significant regenerative potential has proven elusive. Although the process of differentiating ES cells into embryoid bodies recapitulates several early events of pre-implantation embryogenesis, structures associated with proper patterning of paraxial mesoderm, such as somites, notochord, and neural tube, are missing, and thus myogenesis does not occur properly in the ES/EB system. We have recently shown that is possible to circumvent the defective EB environment by over-expressing Pax3, the master regulator of the myogenic program. Accordingly, Pax3 allowed the reprogramming of mesodermal cells not fated to become muscle towards the myogenic cell fate. This strategy in concert with a cell purification method based on paraxial and lateral plate mesoderm surface markers enabled us to generate a teratoma-free early population of myogenic progenitors from ES cells, capable of promoting extensive engraftment of adult myofibers and improvement in contractile function. We are currently assessing the long-term regenerative potential of the cells and whether they seed the satellite cell compartment in vivo. These results will be discussed.
It has been suggested that hematopoietic and endothelial lineages arise in mesoderm from a common bipotent progenitor - the hemangioblast. Intriguingly, bone marrow and peripheral blood from adults have been described as rich sources of endothelial progenitor cells. However, it is still not clear which cell type in these heterogeneous tissues might be preferable for vascular regeneration since studies directly comparing different cell sub-populations are lacking. By combining sub-fractionation of cord blood with a single-cell sorting approach, we have identified a common progenitor for endothelial, myeloid, and lymphoid precursors. The relevance of these findings for regenerative medicine will be discussed.
Rita C. R. Perlingeiro
Lillehei Heart Institute, Department of Medicine,
University of Minnesota, Minneapolis,USA.