Transcriptional Profiling Of The Adult Hair Follicle Mesenchyme Reveals R-spondin As A Novel Regulat

[InBeforeTheCure]

Transcriptional Profiling of the Adult Hair Follicle Mesenchyme Reveals R-spondin as a Novel Regulator of Dermal Progenitor Function

SUMMARY
The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem cells and neighboring mesenchyme. Recent work described the existence of HF dermal stem cells (hfDSCs), but the genetic regulation of hfDSCs and their daughter cell lineages in HF regeneration remains unknown. Here we prospectively isolate functionally distinct mesenchymal compartment in the HF (dermal cup [DC; includes hfDSCs] and dermal papilla) and define the transcriptional programs involved in hfDSC function and acquisition of divergent mesenchymal fates. From this, we demonstrate cross-compartment mesenchymal signaling within the HF niche, whereby DP-derived R-spondins act to stimulate proliferation of both hfDSCs and epithelial progenitors during HF regeneration. Our findings describe unique transcriptional programs that underlie the functional heterogeneity among specialized fibroblasts within the adult HF and identify a novel regulator of mesenchymal progenitor function during tissue regeneration.

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Studies on R-spondin are interesting to us because genetic variants around RSPO2 (R-spondin 2) are among the most impactful in A.G.A. along with AR (Androgen Receptor) and SRD5A2 (5-alpha-reductase type II), so like AR and SRD5A2, R-spondin 2 probably plays a major causal role.

 

[inmyhead]

This is not that new... And impossible to test right now since we can't get it.

https://www.sciencedirect.com/science/article/pii/S0022202X16310545

An ideal anagen-inducing therapy would be effective via topical application, but in this study, we delivered Rspo2 via intradermal injection. Transdermal delivery of a 22 kD hydrophilic protein is impractical (Bos and Meinardi, 2000); therefore, alternative delivery methods would have to be devised. Microneedles porate/permeabilize skin in a relatively noninvasive manner, and might be suitable for this purpose (Hultstrom et al., 2014, van der Maaden et al., 2012). Once into the dermis, Rspo2 would likely have to be protected from degradation by proteolytic enzymes, perhaps by liposomal packaging. Whether such a formulation of Rspo2 remains active within the HF remains to be tested.