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Engineered niches support the development of human dendritic cells in humanized mice
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Engineered niches support the development of human dendritic cells in humanized mice
Creator
Dutertre, Charles-Antoine
Ginhoux, Florent
Newell, Evan
Anselmi, Giorgio
Bourdely, Pierre
Guermonprez, Pierre
Helft,
Hickman, Oliver
Koussou, Missolo
Saxena, Alka
Vaivode, Kristine
Wood, Kristie
Yoann,
Source
BioRxiv
abstract
Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is both crucial to study cDCs and harness their potential in immunotherapy. Here we addressed whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche where they physiologically develop and maintain. We found that expression of the membrane bound form of human FLT3L and SCF together with CXCL12 in a bone marrow mesenchymal stromal cell line is sufficient to induce the contact-dependent specification of both type 1 and type 2 cDCs from CD34+ hematopoietic stem and progenitor cells (HSPCs). Engraftment of these engineered mesenchymal stromal cells (eMSCs) together with CD34+ HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice. Cell-to-cell contact between HSPCs and stromal cells within these organoids drive the local specification of cDCs and CD123+AXL+CD327+ pre/AS-DCs. cDCs generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro generated subsets. Altogether, eMSCs provide a novel and unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo.
has issue date
2019-11-08
(
xsd:dateTime
)
bibo:doi
10.1101/835223
has license
biorxiv
sha1sum (hex)
e8014deacf2ebb6d85682fbe76f8215b1b5b15ec
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https://doi.org/10.1101/835223
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Engineered niches support the development of human dendritic cells in humanized mice
schema:publication
bioRxiv
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covid:e8014deacf2ebb6d85682fbe76f8215b1b5b15ec#body_text
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named entity 'trophic'
named entity 'regulation'
named entity 'CXCL12'
named entity 'human'
named entity 'differentiate'
named entity 'platform'
named entity 'generated'
named entity 'immunodeficient'
named entity 'immunotherapy'
named entity 'delivered'
named entity 'induce'
named entity 'full spectrum'
named entity 'niche'
named entity 'subsets'
named entity 'sentinel'
named entity 'adaptive'
named entity 'human'
named entity 'bone marrow'
named entity 'CD123'
named entity 'type 1'
named entity 'hematopoietic'
named entity 'HSPCs'
named entity 'progenitor cells'
named entity 'CXCL12'
named entity 'mesenchymal'
named entity 'humanized mice'
named entity 'dendritic cells'
named entity 'CD34'
named entity 'TPO'
named entity 'BCL11A'
named entity 'GM-CSF'
named entity 'CyTOF'
named entity 'pDC'
named entity 'CD123'
named entity 'HSPCs'
named entity 'CD14'
named entity 'DCs'
named entity 'transcriptome'
named entity 'cDC'
named entity 'CD163'
named entity 'membrane bound'
named entity 'cDC2'
named entity 'CD141'
named entity 'total protein'
named entity 'HLA-DR'
named entity 'transcriptional'
named entity 'cDC2'
named entity 'phenotypically'
named entity 'DCs'
named entity 'KITL'
named entity 'human blood'
named entity 'immunodeficient'
named entity 'supernatant'
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named entity 'physiological'
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named entity 'Hierarchical clustering'
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named entity 'Illumina'
named entity 'DCs'
named entity 'TCF4'
named entity 'inflammatory'
named entity 'Clec9A'
named entity 'CXCL12'
named entity 'Dimension reduction'
named entity 'microenvironment'
named entity 'membrane-bound'
named entity 'cell interactions'
named entity 'circulating blood'
named entity 'cell cycle'
named entity 'cDC2'
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