Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells.

Abstract:

The study of congenital virus infections in humans requires suitable ex vivo platforms for the species-specific events during embryonal development. A prominent example for these infections is rubella virus (RV) which most commonly leads to defects in ear, heart, and eye development. We applied teratogenic RV to human induced pluripotent stem cells (iPSCs) followed by differentiation into cells of the three embryonic lineages (ecto-, meso-, and endoderm) as a cell culture model for blastocyst- and gastrulation-like stages. In the presence of RV, lineage-specific differentiation markers were expressed, indicating that lineage identity was maintained. However, portrait analysis of the transcriptomic expression signatures of all samples revealed that mock- and RV-infected endodermal cells were less related to each other than their ecto- and mesodermal counterparts. Markers for definitive endoderm were increased during RV infection. Profound alterations of the epigenetic landscape including the expression level of components of the chromatin remodeling complexes and an induction of type III interferons were found, especially after endodermal differentiation of RV-infected iPSCs. Moreover, the eye field transcription factors RAX and SIX3 and components of the gene set vasculogenesis were identified as dysregulated transcripts. Although iPSC morphology was maintained, the formation of embryoid bodies as three-dimensional cell aggregates and as such cellular adhesion capacity was impaired during RV infection. The correlation of the molecular alterations induced by RV during differentiation of iPSCs with the clinical signs of congenital rubella syndrome suggests mechanisms of viral impairment of human development.

PubMed ID: 31405163

Projects: LHA - Leipzig Health Atlas

Publication type: Not specified

Journal: Cells

Human Diseases: No Human Disease specified

Citation: Cells. 2019 Aug 10;8(8). pii: cells8080870. doi: 10.3390/cells8080870.

Date Published: 10th Aug 2019

Registered Mode: by PubMed ID

Authors: N. C. Bilz, E. Willscher, H. Binder, J. Bohnke, M. L. Stanifer, D. Hubner, S. Boulant, U. G. Liebert, C. Claus

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Created: 22nd Apr 2020 at 13:03

Last updated: 7th Dec 2021 at 17:58

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