congrats Mike!

add me pls 🙋🏻‍♂️ thx!

Thanks Akshay! From the atlas we also really appreciate how beautiful and clean LRRC15 is!

pls add me to the cancer immune pack thanks🙏

would love to be added, thanks! 🙏

would love to be added too, thanks! 🙏

8/8) Mechanically, stromal SPP1 KO results in a normalization of myCAF, in which they become more steady-state like and inflammatory, leading to more T cell infiltration, suggesting SPP1 is a key molecule mediating the crosstalk between CAF populations and immune cells.

7/8) We found one of the molecules that are substantially upregulated in both apCAF lineages are SPP1. Stromal KO of SPP1 significantly reduced peritoneal metastasis, ascites formation and pancreatic cancer progression.

6/8) In pancreatic cancer, M-apCAFs are also associated with chemoresistant-cancer epithelium. In addition, we identified two molecular subtypes of peritoneal metastasis, one subtype consistently carries robust TLS and F-apCAFs.

5/8) Interestingly, we found F-apCAF is the major CAF population within TLS, and highly associated with lymphocytes. In contrast, M-apCAFs tend to be tumor epithelium-adjacent. The M-apCAF niches are featured by exhausted or suppressive T cell signatures.

4/8) We exploited two diseases models: pancreatic cancer and peritoneal metastasis derived from colon cancer (a model enriched for both apCAF lineages).

3/8) Based on our scRNA seq atlas, we fully customized a 480 gene panel and ran Xenium spatial assay, through which we identified the distinct niches formed by the two apCAF lineages respectively.

2/8) Surprisingly, we found apCAFs can be derived from two different lineages. One is consistent with what we reported earlier, from mesothelial-like cells (M-apCAF), another is from a speculated blood-origin, carrying a fibrocyte feature (F-apCAF).

1/8) In this study we applied a big data approach and generated a human pan-cancer scRNA seq atlas. First, CAFs are more conserved than we thought across organs. They mostly consist of four molecular subtypes: steady-state like, inflammatory, myofibroblastic, antigen-presenting.