Hfs In Mice Lacking Wnt10a Resemble Androgenetic Alopecia Hfs

[InBeforeTheCure]

WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation

Relevant excerpts:

Adult mice with global or constitutive epithelial Wnt10a deletion displayed increasingly sparse hair with age. HFs undergo periodic cycles of growth (anagen), regression (catagen) and rest (telogen), driven by rarely proliferating epithelial stem cells in the permanent KRT15+ CD34+ bulge region, and rapidly proliferating progenitors in the adjacent KRT15+ CD34− secondary hair germ (SHG)30. Immunofluorescence for pan-hair shaft keratins produced a signal in mutant HFs, and cuticle structure appeared grossly normal by scanning electron microscope (SEM); however, mutant hair shafts were shorter and thinner than controls, with disorganized internal structures (Supplementary Fig. 2a–j). To investigate the mechanisms underlying these defects, we induced epithelial Wnt10a deletion at successive time points in K5-rtTA tetO-Cre Wnt10afl/fl mice. Wnt10a loss from P9 (embryonic anagen) caused premature HF regression, cessation of matrix cell proliferation and decreased cyclin D1 expression (Fig. 5a–b′ and Supplementary Fig. 2k,l). Deletion at P18 delayed initiation of anagen, indicated by histology and absent SHG proliferation (Fig. 5c–d′), and prevented timely TL-GFP activation and external hair growth (Fig. 5k–m). These phenotypes mimicked the effects of Wnt/β-catenin inhibition16. Mutant HFs eventually entered anagen by P29 (Fig. 5e,f), but proliferation and cyclin D1 expression remained lower than in controls (Fig. 5e′ and Supplementary Fig. 2m–p). Wnt10a deletion in full postnatal anagen slightly reduced proliferation but did not cause HF regression (Fig. 5g–i and Supplementary Fig. 2q,r), suggesting compensatory activity of other Wnts. Thus, epithelial WNT10A/β-catenin signalling maintains embryonic anagen and promotes anagen onset.

By 6 months of age, Wnt10a mutant HFs became miniaturized with enlarged sebaceous glands and elevated lipid production (Fig. 5n–s). Dominant negative Lef1 also causes sebaceous gland expansion31, consistent with decreased Wnt/β-catenin signalling in Wnt10a mutant HFs. Despite HF miniaturization in Wnt10a mutants, CD34+ KRT15+ bulge stem cells were retained (Fig. 5t–w). Miniaturized HFs in human androgenetic alopecia similarly display enlarged sebaceous glands and bulge stem cell retention32. As data from genome-wide association studies indicate association of a WNT10A variant with androgenetic alopecia6, decreased WNT10A/β-catenin signalling may contribute to this condition.

In normal aged mice (18–34 months), HFs miniaturize via loss of stem cells due to COL17A1 proteolysis33. Miniaturized HFs of 6-month-old Wnt10a mutants expressed COL17A1 (Supplementary Fig. 2s,t), consistent with maintenance of stem cell markers and suggesting that miniaturization was not caused by accelerated aging. In line with this, levels of Axin2 expression are similar in young and aged HFs33.

Using genetic mouse models, we show that long-term absence of WNT10A causes HF miniaturization and sebaceous gland enlargement, with retention of bulge stem cells. This phenomenon is also observed in human androgenetic alopecia, consistent with identification of a WNT10A variant associated with lower expression levels and male pattern baldness. Functional studies of the WNT10A variant may shed further light on the aetiology of this common condition.

 

[Armando Jose]

Very interesting .....
Wnt10a mutant HFs are miniaturized and sebaceous glands (arrows) enlarged compared to controls at P180. (p–s) Oil-red O (p,q) and FABP5 (r,s) staining reveal increased lipid in Wnt10a mutant HFs compared with controls (arrows).
Bulge stem cell markers KRT15 and CD34 are retained in Wnt10a mutant HFs at P180

 

[GiveMeAccessToMyAccount]

I'm about to start a rap group called Baldies With Attitude and our hit single will by F#%k The Mice.

"F*#k the mice, i'm coming straight from H-L-T ya'll, a young guy got it bad cause i'm bald."

 

[Grasshüpfer]

So it's really the sebums fault!!!!!!!!

 

[Armando Jose]

So it's really the sebums fault!!!!!!!!

Possibly

 

[Balding curse]

I'm about to start a rap group called Baldies With Attitude and our hit single will by F#%k The Mice.

"F*#k the mice, i'm coming straight from H-L-T ya'll, a young guy got it bad cause i'm bald."

And two baldies twerking with their heads.

 

[jphalo]

Does anyone knows how to promote wnt10a ?

 

[Medina]

Does anyone knows how to promote wnt10a ?

Cobain may have predicted it, f*****g genius wasn't even balding

 

[FCKW36]

So it's really the sebums fault!!!!!!!!

Funny thing is, I'm losing hair all over my head and the sebum production on my head is insanely high.

 

[abcdefg]

Yeah dont androgens cause increase in size/activity of sebaceous glands? Im not sure we know though if that is a separate thing from DHT causing male pattern baldness or there is some cause/effect between them. Androgens do cause both to happen though I read that in many places.

 

[InBeforeTheCure]

So it's really the sebums fault!!!!!!!!

Nope. Wnt controls stem cell fate. A high level of Wnt signaling pushes stem cells to become hair follicle progenitors. Without Wnt they become sebocytes. Hence the HF miniaturization and sebaceous gland expansion.

 

[Grasshüpfer]

Hence the HF miniaturization and sebaceous gland expansion.

I just couldn't resist. Sorry for derailing.

That said, do you think that the wnt pathway disruption is a result of the Ar activation.
Or could it be a different pathway, eventually even upstream of the Ar in the chain of events?

Isn't wnt10a the target of Samumed?

 

[FCKW36]

Interesting, thanks to seti I have less sebum production, other people on seti mention the same...

Does Seti stopped hairloss in your case?

 

[Sanchez1234]

Interesting, thanks to seti I have less sebum production, other people on seti mention the same...

Where to get seti?

 

[Trichosan]

Where to get seti?

https://www.seti.org

...the cure is out there.

 

[plisk]

i dont know why people are so quick to dismiss Armando's thoughts about sebum

ever since i started balding my sebum production has increased noticeably and dramatically. To disregard this as some "evolutionary vestige" just seems silly, one should consider all the mechanical changes in the scalp because they're probably relevant.

edit: and fwiw, almost all effective hair loss treatments have a marked effect on sebum production, including finasteride and minoxidil.

 

[Grasshüpfer]

i dont know why people are so quick to dismiss Armando's thoughts about sebum

ever since i started balding my sebum production has increased noticeably and dramatically. To disregard this as some "evolutionary vestige" just seems silly, one should consider all the mechanical changes in the scalp because they're probably relevant.

edit: and fwiw, almost all effective hair loss treatments have a marked effect on sebum production, including finasteride and minoxidil.

Yes but that's really just because sebum is a symptom that comes in very late.
You are not balding because of sebum, but more sebum is produced because you are balding.

My first Sebum!!!! comment was really just trolling.

 

[Medina]

Was on fina for 2 years, had a complete stop of hairloss with that. Stopped because of sides though.

Now on seti for 6+ months (200mg/dag). Have a strong reduction in hairloss. I'll probably start a thread when I'm on the 1 year mark.

Other things I noticed when on seti:

- Strong/ complete stop of itching
- Reduced sebum production
- Noticed some hairloss in "safe zones", sides of head. Could be temporarily, I don't really know.

Are you just on Seti or anything else?

 

[hairblues]

so would this help or is this snake oil?

https://www.haircycle.com/hair-loss-products/wnt-act

here is ingredients
Water (Aqua), Propylene Glycol, Trehalose, , Panthenol, PEG-40 Hydrogenated Castor Oil, Methyl vanillate, Wheat Amino Acids, Soy Amino Acids, Arginine HCL, Serine, Threonine, Niacinamide, Faex Extract, Horse Chestnut (Aesculus Hippocastanum) Extract, Ammonium Glycyrrhizate, Zinc Gluconate, Caffeine, Biotin, Manganese PCA, Disodium EDTA, Sodium Hydroxymethylglycinate, Lactic Acid, Fragrance (Perfume)

 

[Trichosan]

so would this help or is this snake oil?

https://www.haircycle.com/hair-loss-products/wnt-act

here is ingredients
Water (Aqua), Propylene Glycol, Trehalose, , Panthenol, PEG-40 Hydrogenated Castor Oil, Methyl vanillate, Wheat Amino Acids, Soy Amino Acids, Arginine HCL, Serine, Threonine, Niacinamide, Faex Extract, Horse Chestnut (Aesculus Hippocastanum) Extract, Ammonium Glycyrrhizate, Zinc Gluconate, Caffeine, Biotin, Manganese PCA, Disodium EDTA, Sodium Hydroxymethylglycinate, Lactic Acid, Fragrance (Perfume)

Nothing there that many other OTC oral supplements or shampoos don't have and are of questionable effectiveness either. Wasn't familiar with Trehalose but don't see a contribution there at all.
https://en.wikipedia.org/wiki/Trehalose