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Published on: October 18, 2016
Transcriptional profiling of human dendritic cell populations and models--unique profiles of in vitro dendritic cells
Kristina Lundberg1, Ann-Sofie Albrekt, Inge Nelissen
1Department of Immunotechnology, Lund University, Lund, Sweden. kristina.lundberg@immun.lth.se
Insights
In vitro dendritic cell (DC) models show unique transcriptional profiles, closely resembling specific myeloid DC subsets. This research aids in selecting appropriate DC models for immunotherapy and in vitro immune function assays.
Area of Science:
- Immunology
- Cell Biology
- Transcriptomics
Background:
- Dendritic cells (DCs) are key immune orchestrators, but their scarcity necessitates in vitro models for research and immunotherapy.
- The relationship between existing in vitro DC models and primary DC populations is not well understood.
Purpose of the Study:
- To characterize and evaluate the functionality and applicability of common in vitro dendritic cell (DC) models.
- To compare in vitro DC models with primary DC populations using a genome-wide transcriptional analysis.
Main Methods:
- Genome-wide transcriptional profiling was conducted on four in vitro DC models: MUTZ-3-DCs, monocyte-derived DCs, CD34-derived DCs, and Langerhans cells (LCs).
- These models were compared to nine primary human DC populations, including various myeloid DC subsets from blood and tonsils.
Main Results:
- Principal Component Analysis revealed that all in vitro DC models most closely resembled tonsillar myeloid DCs (mDCs), specifically CD1c(+) and CD141(+) subsets.
- No single in vitro model demonstrated superior resemblance to all primary DC populations, suggesting a need for improved differentiation strategies.
- Hierarchical clustering identified distinct gene expression patterns within both model and primary DCs, with model DCs expressing relevant immune transcripts.
Conclusions:
- The distinct transcriptional profiles of in vitro DC models indicate varied functionalities for immune applications.
- These findings will guide the selection of suitable DC models for in vitro assays and support the advancement of DC-based immunotherapy development.
Background:
Dendritic cells (DCs) comprise heterogeneous populations of cells, which act as central orchestrators of the immune response. Applicability of primary DCs is restricted due to their scarcity and therefore DC models are commonly employed in DC-based immunotherapy strategies and in vitro tests assessing DC function. However, the interrelationship between the individual in vitro DC models and their relative resemblance to specific primary DC populations remain elusive.
Objective:
To describe and assess functionality and applicability of the available in vitro DC models by using a genome-wide transcriptional approach.
Methods:
Transcriptional profiling was performed with four commonly used in vitro DC models (MUTZ-3-DCs, monocyte-derived DCs, CD34-derived DCs and Langerhans cells (LCs)) and nine primary DC populations (dermal DCs, LCs, blood and tonsillar CD123(+), CD1c(+) and CD141(+) DCs, and blood CD16(+) DCs).
Results:
Principal Component Analysis showed that transcriptional profiles of each in vitro DC model most closely resembled CD1c(+) and CD141(+) tonsillar myeloid DCs (mDCs) among primary DC populations. Thus, additional differentiation factors may be required to generate model DCs that more closely resemble other primary DC populations. Also, no model DC stood out in terms of primary DC resemblance. Nevertheless, hierarchical clustering showed clusters of differentially expressed genes among individual DC models as well as primary DC populations. Furthermore, model DCs were shown to differentially express immunologically relevant transcripts and transcriptional signatures identified for each model DC included several immune-associated transcripts.
Conclusion:
The unique transcriptional profiles of in vitro DC models suggest distinct functionality in immune applications. The presented results will aid in the selection of an appropriate DC model for in vitro assays and assist development of DC-based immunotherapy.
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