BBB seminar: Seppo J. Vainio
Targeting the program that organizes the stem cells into a nephron, the functional unit of the mammalian kidney
Seppo J. Vainio
Biocenter Oulu, InfoTech Oulu, Center for Cell-Matrix Research, University of Oulu, Finland
To take better use of the embryonic progenitor cells or the cells derived via reprogramming from an adult we need to learn how to set up specific morphogenetic programs to construct functional organs from them. Our laboratory targets mechanisms of mammalian kidney development. The cells that assemble the kidney can be dissected and subjected to ex vivo organ culture that recapitulates the organ assembly process surprisingly well. To address the mechanisms we have advanced the classic embryological methods. The kidney primordia can be prepared and the nephron forming metanephric mesenchyme (MM) can be separated from the epithelial ureteric bud. The MM can be further dissociated to single cells so that they preserve their renal competence. Any progenitor cell type can be extracted from the MM and replaced with corresponding GFP+ ones for fate mapping purposes. Single cells can also be transduced prior to their reaggregation with recombinant retroviruses for knock down or gain of function purposes and yet the organ can be regenerated in 3D from them. The isolated GFP+ nephron founder cells when mixed with non-labeled MM cells memorize their cell fate and nephron composed exclusively from the GFP+ can be obtained to target modes of cell lineage commitment. Finally the primary progenitor cells can be transfected also with siRNAs for gene knock down for more throughput functional studies. In summary the current renal tissue engineering capabilities have enabled functional genetic analysis in the ex vivo setting to reveal molecular details of the nephrogenesis program triggered by Wnt signaling.
Chairperson: Päivi Kettunen, Department of Biomedicine