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Dissecting mechanisms underlying dendritic cell epigenetic reprogramming

Sæmundsdóttir, Svandís Þóra (2019) BINP52 20182
Degree Projects in Bioinformatics
Popular Abstract
Global gene expression of reprogrammed dendritic cells

Cell reprogramming refers to the emergent ability to transform one cell type into another functional cell type. Gene expression gives us insight into the function of a cell, what protein it is producing and what functional pathways it is maintaining. In this project, I analyzed the expression of all genes of dendritic cells (DCs) reprogrammed from mouse and human fibroblasts. Thus, gene expression profiles of reprogrammed DCs gave me a picture of pathways that were activated or silenced when going from fibroblast to DCs.

By analyzing the gene expression at multiple timepoints during the reprogramming of mouse and human fibroblasts, I observed that the process is both gradual and... (More)
Global gene expression of reprogrammed dendritic cells

Cell reprogramming refers to the emergent ability to transform one cell type into another functional cell type. Gene expression gives us insight into the function of a cell, what protein it is producing and what functional pathways it is maintaining. In this project, I analyzed the expression of all genes of dendritic cells (DCs) reprogrammed from mouse and human fibroblasts. Thus, gene expression profiles of reprogrammed DCs gave me a picture of pathways that were activated or silenced when going from fibroblast to DCs.

By analyzing the gene expression at multiple timepoints during the reprogramming of mouse and human fibroblasts, I observed that the process is both gradual and conserved between the two species. The mouse reprogrammed DCs shared gene signature with “natural” DCs and RNA velocity of the human reprogrammed DCs showed them favoring a DC type 1-like fate. Pathway analysis showed the reprogrammed DCs were activating pathways important for DCs maturation, such as antigen uptake and response to inflammation.

The success of reprogramming from fibroblasts to DCs was also confirmed by analyzing the differences between “natural” DCs and reprogrammed DCs. Reprogrammed DCs showed enrichment in pathways related to cell structure, lysosome and autophagy pathways. Enrichment in pathways related to cell structure reflects the dramatic morphological changes fibroblasts undergo to acquire DC shape. Enrichment in lysosome and autophagy pathways imply that the reprogrammed DCs are more stimulated and active in uptake and process of cellular components.

Reprogrammed DCs take up and digest antigen
Pathways that were seen enriched in the reprogrammed DCs revolved around vesicle formation and lysosome. This is consistent with one of DCs main function to engulf foreign antigen and it does so be forming a vesicle from the cell membrane that later fuses with lysosome for degradation. Autophagy was also a pathway that was seen enriched in the reprogrammed DCs. Autophagy and lysosome in DCs are tightly link, with autophagosome being one type of vesicle that fuses with lysosome for degradation. The present of a foreign antigen and inflammation promotes DCs maturation and pathways involving responses to inflammation were also seen enriched in reprogrammed DCs.

Reprogrammed DCs exit the cell cycle and modify their cell structure
Pathways that were silenced in the reprogramming process included cell division and translation. Since DCs are mature blood cells, meaning they don’t divide while fibroblast rapidly divide, it is understandable that pathways involving division are being silenced. Cell structure is very unique in DCs, as they develop dendrites that extend out from their main cell body. Pathways involved in cell structure were up- and downregulated during reprogramming, indicating the reprogrammed DCs are going through structural changes.

Master’s Degree Project in Bioinformatics 60 credits 2019
Department of Biology, Lund University

Advisor: Filipe Pereira
Molecular Medicine and Gene Therapy (Less)
Please use this url to cite or link to this publication:
author
Sæmundsdóttir, Svandís Þóra
supervisor
organization
course
BINP52 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8994923
date added to LUP
2019-09-13 15:31:04
date last changed
2019-09-13 15:31:04
@misc{8994923,
  author       = {{Sæmundsdóttir, Svandís Þóra}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Dissecting mechanisms underlying dendritic cell epigenetic reprogramming}},
  year         = {{2019}},
}