Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response

The homeobox transcription factor Meis1 is required for mammalian development and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease, and tested this using cell lineage tracing and cell specific Meis1 deletion in development, aging and fibrotic disease. We observed strong expression of Meis1 in PDGFRβ positive pericytes and perivascular fibroblasts, both in adult mouse and to a lesser degree in human kidney. Either bilateral ischemia-reperfusion injury (IRI) or aging itself led to strong upregulation of Meis1 protein and mRNA in kidney myofibroblasts, and genetic lineage analysis confirmed that Meis1 positive cells proliferate as they differentiate into myofibroblasts after injury. Conditional deletion of Meis1 in all kidney stroma with two separate CreER drivers had no phenotype with the exception...