Functional genomics of stromal cells in chronic inflammatory diseases.

TitleFunctional genomics of stromal cells in chronic inflammatory diseases.
Publication TypeJournal Article
Year of Publication2018
AuthorsSlowikowski, K, Wei, K, Brenner, MB, Raychaudhuri, S
JournalCurr Opin Rheumatol
Date Published2018 Jan
KeywordsArthritis, Rheumatoid, Cell Differentiation, Chemokines, Endothelial Cells, Fibroblasts, Flow Cytometry, Genomics, Humans, Inflammatory Bowel Diseases, Mesenchymal Stem Cells, Pericytes, Rheumatic Diseases, RNA, Messenger, Sequence Analysis, RNA, Single-Cell Analysis, Stromal Cells, Synovial Membrane, Thy-1 Antigens

PURPOSE OF REVIEW: Stroma is a broad term referring to the connective tissue matrix in which other cells reside. It is composed of diverse cell types with functions such as extracellular matrix maintenance, blood and lymph vessel development, and effector cell recruitment. The tissue microenvironment is determined by the molecular characteristics and relative abundances of different stromal cells such as fibroblasts, endothelial cells, pericytes, and mesenchymal precursor cells. Stromal cell heterogeneity is explained by embryonic developmental lineage, stages of differentiation to other cell types, and activation states. Interaction between immune and stromal cell types is critical to wound healing, cancer, and a wide range of inflammatory diseases. Here, we review recent studies of inflammatory diseases that use functional genomics and single-cell technologies to identify and characterize stromal cell types associated with pathogenesis.

RECENT FINDINGS: High dimensional strategies using mRNA sequencing, mass cytometry, and fluorescence activated cell-sorting with fresh primary tissue samples are producing detailed views of what is happening in diseased tissue in rheumatoid arthritis, inflammatory bowel disease, and cancer. Fibroblasts positive for CD90 (Thy-1) are enriched in the synovium of rheumatoid arthritis patients. Single-cell RNA-seq studies will lead to more discoveries about the stroma in the near future.

SUMMARY: Stromal cells form the microenvironment of inflamed and diseased tissues. Functional genomics is producing an increasingly detailed view of subsets of stromal cells with pathogenic functions in rheumatic diseases and cancer. Future genomics studies will discover disease mechanisms by perturbing molecular pathways with chemokines and therapies known to affect patient outcomes. Functional genomics studies with large sample sizes of patient tissues will identify patient subsets with different disease phenotypes or treatment responses.

Alternate JournalCurr Opin Rheumatol
PubMed ID28984647
PubMed Central IDPMC5890939
Grant ListU01 GM092691 / GM / NIGMS NIH HHS / United States
F31 AR070582 / AR / NIAMS NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
U01 HG009379 / HG / NHGRI NIH HHS / United States
UH2 AR067677 / AR / NIAMS NIH HHS / United States
U01 HG009088 / HG / NHGRI NIH HHS / United States