We applied PHYFUM to 22 patients (colon, small intestine, endometrium). Gut glands diverged early, with most branching happened during childhood/puberty. Endometrial glands showed much more recent divergence, consistent with cyclical glandular renewal 🔄
We then thought what else we could learn with PHYFUM. We implemented four different crypt division models in PHYFUM, and found we have signal in simulated data to detect them.
In our patient data, we found that budding is strongly rejected accross all tissues. Cloning (both daughter crypts end up with the same set of stem cells) is often the preferred model. This is new evidence of symmetric gland fission as possibly the norm in healthy human tissue 🎯
Studying how normal tissues evolve in living humans is incredibly hard. Most phylogenetic methods rely on DNA mutations, but mutation rates are too low to get fine-grained resolution of tissue history. We needed a faster molecular clock ⏱️