We uncovered a pathway that unlinks #regeneration and #tumorigenesis – a discovery with profound implications for #regenerativemedicine. This holds promise for #IBD, #cancer, and beyond!

Next, we explored how is LXR activated endogenously. Revisiting our #transcriptomics datasets from damage-repair models, we uncovered a key player: #CYP27A1, a cholesterol-metabolizing enzyme. It’s induced by damage and acts upstream of LXR – a critical piece of the puzzle!

How does LXR activation inhibit tumorigenesis?
Using longitudinal #bulk & #spatialtranscriptomics, we found LXR bolsters adaptive immunity - supporting B cells & CD8+ T cells to suppress tumor growth.

How does LXR promote regeneration?🤔
Using #scRNAseq and #organoids, we found that LXR induces amphiregulin – an EGFR ligand – in epithelial cells (previously understudied cellular source), to promote regeneration, and was validated with AREG KO mice and neutralizing antibody.

Does it increase tumor risk? 🤔
Unlike other pro-regenerative modulators, LXR activation inhibited tumorigenesis – an #unlinker of #regeneration and #tumorigenesis!

Using #invivo gain and loss-of-function studies and #invitro #organoids, we showed that LXR activation in intestinal epithelial cells (IECs) promotes intestinal regeneration.

We analyzed #transcriptomics datasets from two intestinal regeneration models #DSS and #irradiation and identified a key player: the #LXR pathway.
Activated in response to damage, it hinted at a potential role in promoting regeneration –a function that has not been explored before.

Do you wonder if #regeneration and #tumorigenesis are always linked, or can they be unlinked to maintain tissue homeostasis? 🤔
Excited to share our latest work published in @Nature, where we explore this fundamental question in the #gut!
Link: www.nature.com/articles/s41... 🧵👇