Inducing Hair Follicle Neogenesis With Secreted Proteins Enriched In Embryonic Skin

[InBeforeTheCure]

Inducing hair follicle neogenesis with secreted proteins enriched in embryonic skin

Abstract:

Organ development is a sophisticated process of self-organization. However, despite growing understanding of the developmental mechanisms, little is known about how to reactivate them postnatally for regeneration. We found that treatment of adult non-hair fibroblasts with cell-free extract from embryonic skin conferred upon them the competency to regenerate hair follicles. Proteomics analysis identified three secreted proteins enriched in the embryonic skin, apolipoprotein-A1, galectin-1 and lumican that together were essential and sufficient to induce new hair follicles. These 3 proteins show a stage-specific co-enrichment in the perifolliculogenetic embryonic dermis. Mechanistically, exposure to embryonic skin extract or to the combination of the 3 proteins altered the gene expression to an inductive hair follicle dermal papilla fibroblast-like profile and activated Igf and Wnt signaling, which are crucial for the regeneration process. Therefore, a cocktail of organ-specific extracellular proteins from the embryonic environment can render adult cells competent to re-engage in developmental interactions for organ neogenesis. Identification of factors that recreate the extracellular context of respective developing tissues can become an important strategy to promote regeneration in adult organs.

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[dermrafok]

Inducing hair follicle neogenesis with secreted proteins enriched in embryonic skin

Abstract:



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Thanks for share it.

 

[bboy]

Wow, so we can now pin down inducing HF neogenesis to 3 proteins?

I'm kind of shocked this hasn't been tried before considering we've been struggling with culturing DP cells for about 20 years...

So theoretically are we looking at a new culturing method or an in vivo treatment?

 

[InBeforeTheCure]

Wow, so we can now pin down inducing HF neogenesis to 3 proteins?

Those three proteins can convert ordinary dermal fibroblasts into something like inductive dermal papilla cells, but that's not the end of the story. In most of their experiments, they were using keratinocytes from newborn rats, but they also did one experiment with adult keratinocytes and found that those formed new hair follicles much less efficiently than the newborn rat keratinocytes when combined with the induced DP-like cells.

Skin extracts from E15.5-17.5, the time period when HF morphogenesis is initiated (Figure S1a), induced new HFs from P1 mouse keratinocytes (Figures 1b and 1b'; Figures S1b and S1b'), with highest inductivity at E16.5 (70%). With serial dilution, the E16.5 extract gradually lose its HF inductivity (Figures S1c and S1c'). The E16.5 extract also induced HF neogenesis from adult mouse keratinocytes, albeit at a lower rate (20%) as compared with P1 keratinocytes (Figures S1b and S1b').

With this method, there's still the problem of the keratinocytes. There was another neogenesis study from last year done on mouse cells, and they found that compared to newborn epidermal cells, adult epidermal cells differentiate prematurely in culture. Maybe that has something to do with it.

The biggest difference we observed is that adult cells quickly differentiate in culture. Compared with the newborn culture, in which epidermal differentiation genes become enriched at later stages (D7), many EDC genes start to be enriched from 6 h or day 1 in adult cultures (Fig. 6B and SI Appendix, Fig. S8F), which could be one of the main reasons that cells lose their competence to regenerate hairs and terminally differentiate.

Protein Kinase C (PKC) is an important regulator of epidermal differentiation, so in last year's study they used a PKC inhibitor to stop the keratinocytes from differentiating too early. Maybe then you could use something like the three-protein extract with dermal fibroblasts to produce DP-like cells, and a PKC inhibitor (and perhaps other things?) for some time to maintain the competence of adult keratinocytes for long enough to make more new follicles?

So theoretically are we looking at a new culturing method or an in vivo treatment?

This study was a new culturing method, but for all I know it could be adapted somehow for use in vivo, like with wounding for example.