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Directly reprogrammed renal cells for targeted medicine

Periodic Reporting for period 2 - DiRECT (Directly reprogrammed renal cells for targeted medicine)

Reporting period: 2020-09-01 to 2022-02-28

The DiRECT project aims to understand optimize and use direct reprogramming of renal cells for disease modelling and other applications. We previously identified four genes that can turn one cell type, for example a skin cell, into a different type that resemble those of the kidney. This cell type conversion process is called direct reprogramming. We currently don’t understand enough of how the conversion takes place to better control and optimize the process. In principle, reprogrammed cells could be used to establish patient specific kidney cells that mechanisms of disease or potential treatments could be tested on in the lab.
During the DiRECT project, we have focused on four areas of research. First, we are trying to understand the mechanism behind the cell-type conversion process. We identified key proteins that are necessary in this process. Second, we try to optimize the reprogramming process. Here, we found a number of factors that positively influence the conditions in which reprogramming occurs most efficiently and how successfully reprogrammed cells can best be cultured.
Third, we aim to control the reprogramming process to more specialized cell types. We found factors that would influence the profile of expressed genes towards a certain tubular segment and found a number of non-standard culturing conditions that help to maintain cell specialization and functionality. Fourth, we have established cell models of human genetic kidney conditions. We currently investigate what molecular pathways are dysregulated in these conditions and hope to therapeutically target key players to reduce disease progression.
We expect that the DiRECT project will broaden the application of direct reprogramming to very specific tubular cell types. We expect that this will make the process more useful to answer specific questions about the function of certain cell types and how they are disrupted in renal diseases.
Microscopy image of directly reprogrammed renal tubule cells.