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Using Direct Cell Reprogramming to Uncover Plasmacytoid Dendritic Cell Specification Programs and Function

Altman, Abigail (2021) MOBN03 20202
Degree Projects in Molecular Biology
Popular Abstract
Using direct cell reprogramming to induce functional plasmacytoid dendritic cells from fibroblasts

Direct cell reprogramming is a technique used to generate differentiated cells of one lineage from somatic cells of another. This concept has been used to explore the diversity and function of numerous cell types. Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells specialized at producing type I interferons (IFN-I). Unlike other dendritic cell subsets, it is still not fully understood how pDCs are generated during development. The aim of this study is to define the proteins or transcription factors (TFs) that regulate the expression of genes required to induce functional pDCs from unrelated cell-types, through cell fate... (More)
Using direct cell reprogramming to induce functional plasmacytoid dendritic cells from fibroblasts

Direct cell reprogramming is a technique used to generate differentiated cells of one lineage from somatic cells of another. This concept has been used to explore the diversity and function of numerous cell types. Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells specialized at producing type I interferons (IFN-I). Unlike other dendritic cell subsets, it is still not fully understood how pDCs are generated during development. The aim of this study is to define the proteins or transcription factors (TFs) that regulate the expression of genes required to induce functional pDCs from unrelated cell-types, through cell fate reprogramming approaches.

A total of 37 candidate TFs were screened to see which combinations were capable of activating lineage-specific reporters. From these screens, a minimal TF combination of IRF8 and SPIB were identified as capable of inducing reporter activation. Building on top of this foundation, a third TF completed the optimal TF combination based on reporter activation, surface marker expression, and cytokine secretion abilities. This trifecta of TF-induced cells express surface markers characteristic to pDCs, including CD45, BST2, MHC-II, B220, Ly6C, and CCR9 (Fig. 1). Importantly, the induced pDCs were capable of secreting IFN-I as well as inflammatory cytokines like TNF-α, IL-6, CCL5, and CXCL10, in response to TLR stimuli (Fig. 1). This finding further supports the idea that the combination of 3 TFs imposes pDC fate in non-related cell types.

In this study, reprogramming was used to identify the transcriptional regulators necessary for the acquisition of pDCs. This provides insight into the development and properties of pDCs. In the past, cell fate reprogramming approaches have been used to generate cells for regenerative medicine purposes. Since pDCs have a critical role in the antiviral response, they are a key cell to examine for immunotherapeutic approaches.

Master’s Degree Project in Molecular Biology, 60cr, Department of Biology, Lund University

Advisors: Filipe Pereira and Cristiana Pires, Department of Molecular Medicine and Gene Therapy, Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Altman, Abigail
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9057797
date added to LUP
2021-06-22 14:46:31
date last changed
2021-07-07 14:50:41
@misc{9057797,
  author       = {{Altman, Abigail}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Using Direct Cell Reprogramming to Uncover Plasmacytoid Dendritic Cell Specification Programs and Function}},
  year         = {{2021}},
}