OSR1 and SIX2 drive divergent transcriptional programs in human kidney cells: implications for regeneration and tumorigenesis

Our findings suggest that <i>SIX2</i> overexpression in primary hAK cells functionally confers enhanced self-renewal and tubulogenic capacity while transcriptionally inducing a proximal-to-distal tubular cell diversion with maintained proliferative programs. In contrast, <i>OSR1</i> activates the broader developmental morphogenetic networks but poses potential oncogenic risks. The malignant transformation observed with <i>OSR1</i> overexpression provides insights into the potential cellular origins of Wilms' tumor and raises important safety considerations for regenerative medicine approaches involving developmental gene induction in adult kidney cells.