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Human DC3 Antigen Presenting Dendritic Cells From Induced Pluripotent Stem Cells
Taiki Satoh1,2,3, Marcelo A S Toledo1,2,4, Janik Boehnke1,2
1Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
Frontiers in Cell and Developmental Biology
|August 9, 2021
Summary
Induced pluripotent stem cells generate human dendritic cells (DC) that mimic blood DC3. These cells effectively polarize T cells and reveal how JAK2 V617F mutations impact DC3 development and function.
Area of Science:
- Immunology
- Stem Cell Biology
- Hematology
Background:
- Dendritic cells (DCs) are crucial antigen-presenting cells derived from hematopoietic stem cells.
- The proinflammatory DC3 subset plays a key role in polarizing CD8+ T cells into tissue-resident memory T cells.
- Induced pluripotent stem cells (iPSCs) offer a model for generating specific cell types for research.
Purpose of the Study:
- To generate human DC3 cells from iPSCs.
- To characterize iPSC-derived DC3 cells.
- To investigate the impact of the JAK2 V617F mutation on DC3 development and function.
Main Methods:
- Differentiation of human iPSCs into DC3 cells.
- Analysis of gene expression and surface markers of iPSC-derived DC3.
- Co-culture of iPSC-derived DC3 with CD8+ T cells.
- Generation of JAK2 V617F mutant DC3 from patient-specific iPSCs.
Main Results:
- iPSC-derived DC3 cells exhibit gene expression and surface markers consistent with blood DC3.
- iPSC-derived DC3 cells effectively polarize CD8+ T cells into CD8+ CD103+ tissue-resident memory T cells in vitro.
- The JAK2 V617F mutation enhances DC3 production and skews differentiation towards erythrocytes and megakaryocytes.
Conclusions:
- Human iPSC-derived DC3 cells serve as a valuable model for studying DC3 biology.
- This model allows for the investigation of DC3 in human diseases, particularly those involving JAK2 V617F mutations.
- Patient-specific iPSC-derived DC3 cells can aid in developing novel therapeutic strategies.
