Thread by @Josh_Currie1

Hey Everyone!
Wanted to do a quick thread summarizing our latest work @biorxivpreprint
We went looking for regenerative cells in mammals and stumbled onto a small, but potent, group of cells in the mouse skin -

https://twitter.com/bxv_dev/status/1086406768605855744

1/ Exciting work out there suggests that our tissues are heterogenous mixtures of cells from different origins, differentiation states, in different niches, etc. Related to regeneration/wound healing - some bad actors may be intrinsically fibrotic
science.sciencemag.org/content/348/62…

2/ We hypothesized that pro-regenerative cells might retain markers that are on in embryonic progenitors or be active in regeneration-competent animals (aka #axolotl)

3/ We looked specifically at an enhancer upstream of the transcription factor Prrx1. This enhancer was characterized by Logan and Tabin in 2002 and labels lateral plate mesoderm progenitors, including limb bud mesenchyme.
onlinelibrary.wiley.com/doi/abs/10.100…

4/ We hooked the Prrx1 enhancer to an inducible Cre (+Teal FP, TFP) so that we could take snapshots across embryonic and adult stages of any cells that had active enhancer expression.

5/ Although everything looked great in the embryo, shortly after birth the number of cells that we could convert dropped dramatically, so that by adulthood we only labelled a teeny, tiny fraction of cells in the skin dermis ( <1% !!).

6/ Curiously, the cells actively expressing the enhancer turned up in very particular niches - in the perivascular space wrapped around blood vessels and in the mesenchymal part of the hair follicle. Others have described stem-like properties for cells from these locales.

7/ The real surprise came after injury. Two weeks following conversion, we made full-thickness skin wounds to limbs. We observed a large enrichment of enhancer cells in the wound bed. A 16 fold increase from the uninjured!! Sadly, they're still a small minority of wound cells 😢

8/ Looking under the skin we got a second surprise. There were a ton of labelled cells incorporated into subcutaneous tissue directly underneath the wound! We hypothesize that the labelled cells originated from the dermis.

9/ The enhancer cells take up new fates such as converting into adipocytes, suggesting that they have multipotent potential.

10/ A few other bullets for the sake of brevity:
- 4 wks post wounding, the # of enhancer cells drops towards uninjured levels

- Long term labelling showed that enhancer cells don't participate in normal tissue turnover, just injury

11/
- exogenous Wnt (to restore a more neonatal environment) doesn't boost the # enhancer cells

- The injury response of enhancer cells is only observed in the limb and not the back skin, which is the common site for most studies (importance of positional information!)

12/
Thanks for reading until the end! Please let us know if you have any feedback or suggestions!
biorxiv.org/content/early/…