Abstract 228: Transcriptional Networks Involved in Differentiation of Renal Progenitor Cells to the Juxtaglomerular Cell Fate
| Autor: | Jose A Gomez, Jennifer Chien, Samantha Jameson, Tilanthi Jayawardena, Romelia Perez-Marco, Yanqiang Yang, Conrad Hodgkinson, Blanche Capel, Victor J Dzau, Maria Mirotsou |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Hypertension. 60 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Background: The molecular processes regulating the development of renin producing juxtaglomerular (JG) cells are not fully understood. We have previously shown that LXRα and cAMP treatment can induce mesenchymal stromal cells (MSCs) from different sources to differentiate into renin expressing JG-like cells. Here, we investigated the LXRα/cAMP induced transcriptional networks involved in the commitment of progenitor cells to the JG lineage. METHODS: Adult renal CD44+ MSCs were isolated from C57BL/6 Ren1c YFP mice. MSCs were differentiated into YFP+ renin expressing cells by treatment with LXRα ligand (T0901317) or cAMP. The Affymetrix Mouse 430 2.0 array was used for profiling. Data analysis was focused on transcriptional and epigenetic regulators and performed by using Dchip, David or Toppgene. Results: Differentiated YFP+ cells from either cAMP or LXRα treatment expressed high levels of renin and renin regulators such as Hoxd8 and Cebp. Untreated MSCs showed expression of metanephric markers such as Foxd1, Sox11 and Eya. Treatment with cAMP resulted in differential expression of 108 transcripts in YFP+ cells as compared to control MSC. The majority of these genes (82) were down-regulated and involved in chromatin acetylation (23 out of 82, P Conclusion: Our data indicate that cAMP and LXRα, rather than directly define JG cell fate, modulate the epigenetic status of MSCs and prevent differentiation to other lineages. Systems biology approaches are under way to evaluate the importance of the transcriptional networks identified. We anticipate that these results will provide novel insights into the mechanisms regulating JG cell fate. |
| Databáze: | OpenAIRE |
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