High dimensional analysis of the human dendritic cell network : discovery of a novel transitional dendritic cell population related to plasmacytoid dendritic cells
Abstract/Contents
- Abstract
- As the professional antigen-presenting cells of the immune system, dendritic cells (DCs) are unique in their capacity to modulate a broad range of immune responses. Their ability to enact such diverse outcomes is mediated by a division of labor among functionally specialized subsets, including plasmacytoid DCs (pDCs) and two subsets of classical DCs, cDC1 and cDC2. Plasmacytoid DCs have been attributed a role in both type-I interferon production and antigen presentation. However, it remains poorly understood how pDCs enact these two functions. Here, we applied cutting edge high-dimensional approaches to analyze the human DC network with the goal of understanding the functional diversity within pDCs. First, we used mass cytometry (CyTOF) and identified a novel population of DCs with a continuum of phenotypes between pDCs and cDCs, which we named transitional DCs (tDCs). Next, we identified the murine equivalent of human tDCs and found evidence of their developmental connection with pDCs. Finally, we used the assay for transposase accessible chromatin using sequencing (ATAC-seq) to profile the chromatin accessibility landscape of primary human DCs, including tDCs and stimulated pDCs. We conclude that tDCs are an evolutionarily conserved DC population that is closely related to pDCs. Independently of the tDC population, we found that pDC functional heterogeneity arises from their capacity for cellular plasticity. Altogether, these findings reveal new insights into DC biology that are critical for the rational design of therapeutics that harness these specialized cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Leylek, Rebecca Ani |
|---|---|
| Degree supervisor | Idoyaga, Juliana |
| Thesis advisor | Idoyaga, Juliana |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Habtezion, Aida |
| Thesis advisor | Schneider, David (David Samuel) |
| Degree committee member | Engleman, Edgar G |
| Degree committee member | Habtezion, Aida |
| Degree committee member | Schneider, David (David Samuel) |
| Associated with | Stanford University, Program in Immunology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Rebecca Ani Leylek. |
|---|---|
| Note | Submitted to the program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Rebecca Ani Leylek
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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