Single-cell transcriptomic analysis of human colonic macrophages reveals niche-specific subsets.
Diana DomanskaUmair MajidVictoria T KarlsenMarianne A MerokAnn-Christin Røberg BeitnesSheraz YaqubEspen Sønderaal BækkevoldFrode Lars JahnsenPublished in: The Journal of experimental medicine (2022)
Macrophages are a heterogeneous population of cells involved in tissue homeostasis, inflammation, and cancer. Although macrophages are densely distributed throughout the human intestine, our understanding of how gut macrophages maintain tissue homeostasis is limited. Here we show that colonic lamina propria macrophages (LpMs) and muscularis macrophages (MMs) consist of monocyte-like cells that differentiate into multiple transcriptionally distinct subsets. LpMs comprise subsets with proinflammatory properties and subsets with high antigen-presenting and phagocytic capacity. The latter are strategically positioned close to the surface epithelium. Most MMs differentiate along two trajectories: one that upregulates genes associated with immune activation and angiogenesis, and one that upregulates genes associated with neuronal homeostasis. Importantly, MMs are located adjacent to neurons and vessels. Cell-cell interaction and gene network analysis indicated that survival, migration, transcriptional reprogramming, and niche-specific localization of LpMs and MMs are controlled by an extensive interaction with tissue-resident cells and a few key transcription factors.
Keyphrases
- single cell
- endothelial cells
- peripheral blood
- induced apoptosis
- network analysis
- transcription factor
- rna seq
- oxidative stress
- cell therapy
- cell cycle arrest
- squamous cell carcinoma
- depressive symptoms
- pluripotent stem cells
- patient safety
- dna methylation
- endoplasmic reticulum stress
- spinal cord injury
- quality improvement
- young adults
- copy number
- squamous cell
- signaling pathway
- subarachnoid hemorrhage
- heat shock
- cerebral ischemia
- neural network