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Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype.

ABSTRACT: The importance of monocyte-derived dendritic cells (DCs) is evidenced by the fact that they are essential for the elimination of pathogens. Although in vitro DCs can be generated by treatment of monocytes with GM-CSF and IL-4, it is unknown what stimuli induce differentiation of DCs in vivo. CD137L-DCs are human monocyte-derived DC that are generated by CD137 ligand (CD137L) signaling. We demonstrate that the gene signature of in vitro generated CD137L-DCs is most similar to those of GM-CSF and IL-4-generated immature DCs and of macrophages. This is reminiscent of in vivo inflammatory DC which also have been reported to share gene signatures with monocyte-derived DCs and macrophages. Performing direct comparison of deposited human gene expression data with a CD137L-DC dataset revealed a significant enrichment of CD137L-DC signature genes in inflammatory in vivo DCs. In addition, surface marker expression and cytokine secretion by CD137L-DCs resemble closely those of inflammatory DCs. Further, CD137L-DCs express high levels of adhesion molecules, display strong attachment, and employ the adhesion molecule ALCAM to stimulate T cell proliferation. This study characterizes the gene expression profile of CD137L-DCs, and identifies significant similarities of CD137L-DCs with in vivo inflammatory monocyte-derived DCs and macrophages.

SUBMITTER: Harfuddin Z

PROVIDER: S-EPMC4949477 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype.

Harfuddin Zulkarnain Z Dharmadhikari Bhushan B Wong Siew Cheng SC Duan Kaibo K Poidinger Michael M Kwajah Shaqireen S Schwarz Herbert H

Scientific reports 20160719

The importance of monocyte-derived dendritic cells (DCs) is evidenced by the fact that they are essential for the elimination of pathogens. Although in vitro DCs can be generated by treatment of monocytes with GM-CSF and IL-4, it is unknown what stimuli induce differentiation of DCs in vivo. CD137L-DCs are human monocyte-derived DC that are generated by CD137 ligand (CD137L) signaling. We demonstrate that the gene signature of in vitro generated CD137L-DCs is most similar to those of GM-CSF and ...[more]

PMID: 27431276

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Project description:The lung mesenchyme gives rise to multiple distinct lineages of cells in the mature respiratory system, including smooth muscle cells of the airway and vasculature. However, a thorough understanding of the specification and mesenchymal cell diversity in the human lung is lacking. We completed single-cell RNA sequencing analysis of fetal human lung tissues. Canonical correlation analysis, clustering, cluster marker gene identification and t-distributed stochastic neighbour embedding representation was performed in Seurat. Cell populations were annotated using ToppFun. Immunohistochemistry and in situ hybridisation were used to validate spatiotemporal gene expression patterns for key marker genes. We identified molecularly distinct populations representing "committed" fetal human lung endothelial cells, pericytes and smooth muscle cells. Early endothelial lineages expressed "classic" endothelial cell markers (platelet endothelial cell adhesion molecule/CD31 and claudin 5), while pericytes expressed platelet-derived growth factor receptor-β, Thy-1 membrane glycoprotein and basement membrane molecules (collagen IV, laminin and proteoglycans). We observed a large population of "nonspecific" human lung mesenchymal progenitor cells characterised by expression of collagen I and multiple elastin fibre genes (ELN, MFAP2 and FBN1). We closely characterised the diversity of mesenchymal lineages defined by α2-smooth muscle actin (ACTA2) expression. Two cell populations, with the highest levels of ACTA2 transcriptional activity, expressed unique sets of markers associated with airway or vascular smooth muscle cells. Spatiotemporal analysis of these marker genes confirmed early and persistent spatial specification of airway (HHIP, MYLK and IGF1) and vascular (NTRK3 and MEF2C) smooth muscle cells in the developing human lung. Our data suggest that specification of distinct airway and vascular smooth muscle cell phenotypes is established early in development and can be identified using the markers we provide.

Dataset Information

Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype.

Publications

Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype.

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