Induction of differentiation in cultured rat and human podocytes

Peter Mundel, Jochen Reiser, Wilhelm Kriz

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

Abstract

Mature podocytes are highly differentiated cells that are unable to divide in vivo. During glomerulogenesis, podocytes develop from simple cuboidal cells into their adult phenotype, which is characterized by a complex pattern of processes. Cultivation of podocytes under standard conditions leads to dedifferentiation, including the loss of processes and of pp44, a marker of differentiated podocytes. In this study, the cell culture conditions for rat and human podocytes were modified by avoiding repeated subcultivation. This led to profound phenotypic changes in podocytes in vitro. The conversion of cobblestones into arborized cells was directly observed, and a series of intermediate phenotypes was documented. The cells converted within 3 wk from typical cobblestone appearance into individual arborized cells more closely resembling in vivo podocytes. Arborized cells were frequently binucleated and reached a size of up to 500 μm. Both cobblestone and arborized cells originated from podocytes, as evidenced by the expression of a podocyte-specific O-acetylated ganglioside and of the WT-1 protein. In contrast to primary cultures and early passages of cobblestones, a cloned rat podocyte cell line did not express WT-1 and could not be induced to differentiate into arborized cells. This finding indicates a role for WT-1 in maintaining differentiation of adult podocytes. The differentiation of arborized cells led to growth arrest and was reflected by the formation of processes and the expression of pp44 and desmin, which were never detected in cobblestones. It was concluded that partial differentiation of cultured podocytes can be achieved simply by avoiding repeated subcultivation, resulting in an arborized phenotype more closely reflecting in vivo podocytes.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalJournal of the American Society of Nephrology
Volume8
Issue number5
StatePublished - May 1997
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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