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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 27, 2023 |
| Title |
Monocytes differentiate into macrophages or dendritic cells along two alternative paths controlled by distinct regulatory networks |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
During inflammation, monocytes differentiate within tissues into macrophages (mo-Mac) or dendritic cells (mo-DC). Whether these two progenies derive from alternative differentiation pathways or represent different stages along a continuum remains unclear. Here we addressed this question using temporal single-cell RNA sequencing in an in vitro model allowing the simultaneous differentiation of human mo-Mac and mo-DC. We evidenced divergent differentiation paths, with a fate decision occurring within the first 24 hours. We confirmed this result in vivo using a mouse model of peritonitis. Using a computational approach, we identified candidate transcription factors potentially involved in monocyte fate commitment. We demonstrated that IRF1 is necessary for mo-Mac differentiation, independently of its transcriptional control of interferon-stimulated genes. In addition, we validated the transcription factors ZNF366 and MAFF as regulators of mo-DC development. Our results indicate that mo-Mac and mo-DC represent two alternative cell fates requiring distinct transcription factors for their differentiation.
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| Overall design |
Kinetic of monocyte differentiation by scRNAseq. We performed scRNAseq of monocytes cultured with a cytokine cocktail that yields to the differentiation of monocytes-derived macrophages and dendritic cells. We combined this technology to HASH-sequencing in order to measure these data simultaneously in two healthy human donors and at different time points.
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| Web link |
https://www.embopress.org/doi/full/10.15252/embr.202256308
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| Contributor(s) |
Villar J, Segura E |
| Citation(s) |
37191947 |
| Submission date |
Nov 21, 2022 |
| Last update date |
Jun 26, 2023 |
| Contact name |
Javiera Villar |
| E-mail(s) |
javillar22@gmail.com
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| Organization name |
Institut Curie
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| Street address |
25 rue d'Ulm
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| City |
Paris |
| ZIP/Postal code |
75005 |
| Country |
France |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA903917 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE218483_RAW.tar |
231.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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