HCA Gut Cell Atlas v1 Myeloid Lineage

I suggest to rename Granulocytes Mast Cells into Mast cells (example: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1494025/full)

• PLA2G2D+ macrophages:
  • PLA2G2D
  • PTGDS
  • MMP9
• C1QC+FOLR2+ macrophages:
  • C1QC
  • FOLR2
  • DNASE1L3
  • ADAMDEC1

Cluster 14 in Leiden: PLA2G2D+ macrophages are an independent group of macrophages characterised by the expression of PLA2G2D, PTGDS, MMP9, described in Gudiño V et al. DOP87: Pathologic fibroblasts and macrophages in colonic Crohn’s disease via spatial transcriptomics. J Crohns Colitis. 2024;18(Suppl 1):i235–i236. Manuscript in process. Clusters 1, 6 and 7 would then be the tissue resident macrophages

• cDC2:
  • CD207
  • CD1C
  • IRF4
• DC3-like:
  • CD14
  • C1QA

Cluster 2_2 seems to be DC2-like but with some macrophage/monocyte marker genes and so aligns with DC3 (although this is a possibly contentious split) https://www.science.org/doi/10.1126/sciimmunol.adz8650

• Classical Monocytes:
  • VCAN
  • FCN1
  • S100A8
  • S100A9
• Non-classical Monocytes:
  • FCGR3A
  • CX3CR1

CD16+ Non-classical monocytes (probably contaminants from blood)

CD14, VCAN, S100...

• FOLR2+ macrophages:
  • FOLR2
  • C1QC
  • CD163L1
• FOLR2+LYVE1+ macrophages:
  • LYVE1
  • FOLR2
  • C1QC
  • CD163L1

Considering the Leiden clustering, I would split M2 macs into clusters 8 and 9, with 8 being FOLR2+ and 9 being FOLR2+LYVE1+. FOLR2+LYVE1+ macrophages may be perivascular macrophages, whereas FOLR2+ macrophages may be found predominantly at the lamina propria.

I suggest to rename Macrophages M2 into C1q+ macrophages. They are driven by C1Q+ genes. Nomenclature M2 is outdated. Here u have example https://www.sciencedirect.com/science/article/abs/pii/S2405803322000425

• RORgt+ DCs:
  • RORC
  • PRDM16
• Doublets:
  • CD2
  • CD79B

These are the recently discovered RORgt+ DCs involved in induction of pTreg https://www.cell.com/cell/fulltext/S0092-8674(25)00293-4 https://www.science.org/doi/10.1126/sciimmunol.adz8650

This seems a contamination cluster with lymphocytes, mostly composed of T cells. Check out top-hits. E.g. different CD3-related genes. Also some B cells/plasma cells, e.g. MZB1 is also a top hit. Remove from this object?

I agree that these are clearly follicular dendritic cells (FDCs). CR1, CR2, FDCSP, CXCL13 etc. https://rupress.org/jem/article/221/1/e20221220/276440/Protective-fibroblastic-niches-in-secondary HOWEVER: This is - despite of the confusing name - a fibroblast subset and should be integrated with the stromal cell object, where they will most likely cluster together with the other fibroblastic reticular cells. These cells have very little in common with myeloid cells.

They are granulocytes; however, I think it can be refined to be eosinophils as they express CLC (top marker), IL4... (Melon-Ardanaz, E 2025).