David Angeles
davidangeles.bsky.social
David Angeles
@davidangeles.bsky.social
Focused on developing molecular technologies to control cell fate with precise spatiotemporal resolution. Recovering computational geneticist, ex-Altos, ex-eGenesis. Caltech PhD.
My biggest question: he showed a regeneration suppression program that is AP polarized. How does this work when injuries happen at the P end? What about lateral injuries? Is there a lateral program?
June 13, 2025 at 1:39 AM
He shows that in planarian species that cannot regenerate, knocking down these “regeneration suppressors” restores their ability to regenerate. Awesome.
June 13, 2025 at 1:38 AM
Next he did a screen and found genes that mediate this suppression in the tail allegedly. claims they are working through regulating differentiated tissue turnover
rates.
June 13, 2025 at 1:38 AM
ok. what does this systemic response do and why is it needed?

He performed a smart series of cutting experiments to show an inhibitory program of regeneration is likely encoded in the posterior segment and is erk mediated.
June 13, 2025 at 1:38 AM
how does the injury passage through the body? in cases of Anterior wounds, it’s through Erk signaling using the longitudinal muscles. unclear how he showed that. I was pretty far away and the talk went by fast.
June 13, 2025 at 1:34 AM
planarians have stem cells known as neoblasts. really cool cells. bo is talking about planarians regeneration. however, only proximal neoblasts to the wound activate initially. later, the rest of the body activates a secondary response. I missed what "activation" entails.
June 13, 2025 at 1:33 AM
She said humans dont have a recognizable blastema. I am not sure why she is saying that… blastema to me means regenerative, proliferative tissue, i don't know if blastemas have a molecular/cellular definition (missing in humans).

Fascinating study of human regeneration.

#isscr2025
June 13, 2025 at 1:31 AM
mass spec of exudate shows different proteins secreted at different stages

an important point is that is that re-epithelialization happens at the end of regeneration. in axolots, it happens earlier, after coagulation.
June 13, 2025 at 1:29 AM
coagulation is early and closes wound. next, fingers grow a granular tissue that looks raw, blistery. in proliferation we see more normal growth but the shape and texture is all wrong. the final stage reconfigures the finger to form the correct structures and final cell types.
June 13, 2025 at 1:29 AM
They identified four different stages of regrowth: coagulation, hypergranulation, proliferation and epithelialization.
June 13, 2025 at 1:28 AM
Note: she pointed out antibiotics are unnecessary because the regenerative program involves a lot of immune mobilization, highly antibacterial!

A leading hypothesis for the limits of regeneration has been immunity--this throws a bit of a wrench in that.
June 13, 2025 at 1:27 AM
wow. they set up a program to recruit injured folks to a trial where they collected exudate, encased the finger in a transparent casing, and where the injury was neither disinfected nor antibiotic treated. 2 sets of xrays for fingertips.
June 13, 2025 at 1:26 AM
salamanders can regrow limbs in 40 days. upon amputation, the wound closes quickly. then it forms an apical epithelial cap, under which is a proliferative tissue, this tissue forms the blastema, and the regeneration program is on.

Note: human fingertips can regenerate even in older folks.
June 13, 2025 at 1:25 AM
now… do they proliferate in injury settings? EdU pulse! And yea! these cells proliferate post injury especially at 28D post injury. Beautiful work and ongoing.
June 13, 2025 at 1:24 AM
They found some tiny muscle cells stain for pax7, right morphology for stem cells, developed tools to study them (found an ab). now isolating them they have proliferative and stem cell characteristics
June 13, 2025 at 1:24 AM