Jornal de pesquisa e terapia com células-tronco

Abstrato

Mesenchymal Stromal Cells and Vascular Morphogenesis: Gene Expression Profiles and Promoting Pathways

Rogier T. A. Van Wijck

ABSTRACT
Objective: Hematopoietic cells and mesenchymal stromal cells are closely related to endothelial cells in the
embryological cell differentiation lineages. To study the pathobiology of vascular immunology and microenvironment
in vascular morphogenesis, we analyzed the genetic factors known to be involved in vascular anomalies in humans
and mice in the expression data from the Immunological Genome Project (ImmGen).
Methods: We mined the Pictures of Standard Syndromes of Undiagnosed Malformations and NCBI Online
Mendelian Inheritance in Man databases to construct a gene list related to vasculature. We studied the expression
signatures of these genes in the ImmGen database. Hierarchical clustering analyses were performed using Partek®
Genomics Suite 6.6. Next, the acquired clusters were separately investigated within Ingenuity Pathway Analysis
(IPA). Based on these results we performed a Principal Component Analysis (PCA) with pericyte samples from a
separate database to investigate the relation with pericytes.
Results: Our database queries resulted in a gene list of 438 genes related to vasculature, of which 384 could be
studied within the ImmGen data set. Through hierarchical clustering we identified five distinct clusters of which
one was specific for expression in mesenchymal cell lines. Next, using IPA we found various pathways related to
pericyte functions. A subsequent PCA with pericyte samples showed a close resemblance to specific stromal cells of
mesenchymal origin indicating shared expression profiles for vascular genes between pericytes and these cell types.
These results indicate that the processes of Epithelial-Mesenchymal-Transition and or Endothelial-Mesenchymal-
Transition underly the interaction between epithelial/endothelial cells and mesenchymal stromal cells in vascular
morphogenesis.
Conclusion: In this data analysis study, we performed data fusion from various sources that may aid future
mechanistic and therapeutic studies in study design and cell type selection as well as provide a potential strategy
to find therapeutic targets based on the specific pathological molecular mechanisms related to vascular anomalies.