Role of Wnt-4 signaling in dendritic cells lineage and differentiation
| Autor: | Pooja Jain, Christopher Scharer, Yuka Kawasawa, Sreesha Sreedhar, Zafar Khan, Jeremy Boss |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 196:52.3-52.3 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.196.supp.52.3 |
| Popis: | Dendritic cells (DCs) are important mediators of the innate and adaptive immune responses. The network of genes governing the differentiation of these cells has been a topic of discussion for a long time, mainly because of their similarity to other myeloid lineages such as monocytes and macrophages. In order to gain insights into the characterization of factors that contribute to the lineage restricted progenitors in the bone marrow that govern DC differentiation, we performed epigenetic analyses utilizing next generation sequencing of bone marrow-derived CD11c+ DCs (BMDCs). Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic growth factor that is crucial to the development and commitment of DCs from the common myeloid progenitor (CMP) to the common dendritic progenitor (CDP), subsequently yielding conventional and plasmacytoid DCs. The combined analysis of the DNA methylome by Reduced Representation Bisulfite sequencing (RRBS) and the transcriptome by RNA-seq identified a hypermethylation and a reduction in gene expression of Wnt-4 signaling. Wnt-4 gene family is implicated in several developmental processes especially in determination of cell fate and embryogenesis. A comparative validation analyses at RNA and protein levels on BM cells, CMPs and BMDCs yielded confirmed changes in Wnt-4 and in another cell-cycle factor, Cyclin-D1. Further studies are being done to identify intersection of DNA methylation/RNA-seq data to see if changes in methylation are correlated with transcription, in the Wnt signaling enabling us to further understand the differentiation and maturation of DC lineages. |
| Databáze: | OpenAIRE |
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