Hair Follicles’ Transit-amplifying Cells Govern Concurrent Dermal Adipocyte Production Through Shh

[InBeforeTheCure]

Hair follicles’ transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog

Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH). Depletion of Shh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion of Smo, a gene required in SHH-receiving cells, we found that SHH does not act on hair follicles, adipocytes, endothelial cells, and hematopoietic cells for adipogenesis. Instead, SHH acts directly on adipocyte precursors, promoting their proliferation and their expression of a key adipogenic gene, peroxisome proliferator-activated receptor γ (Pparg), to induce dermal adipogenesis. Our study therefore uncovers a critical role for TACs in orchestrating the generation of both their own progeny and a neighboring lineage to achieve concomitant tissue production across lineages.

Full text attached.

 

[ahmad029]

and you cannot up regulate Shh because it may cause cancer, some time i thought that our body losses hair in order to prevent cancer.
shh, wnt etc all posses proliferative properties on the other hand Dkk-1 and others are pro-appoptotic substances.

 

[Swoop]

https://www.researchgate.net/public..._directly_repressing_the_Hh_signaling_pathway

Hair follicles (HFs) undergo precisely regulated cycles of active regeneration consisting of (anagen), involution (catagen), and relative quiescence (telogen) phases. HF stem cells (HFSCs) play important roles in regenerative cycling. Elucidating mechanisms that governs HFSC behavior can help uncover the underlying principles of hair development, hair growth disorders and skin cancers. RNA-binding proteins of the Musashi (Msi) have been implicated in the biology of different stem cell types, yet they have not been studied in HFSCs. Here we utilized gain- and loss-of-function mouse models to demonstrate that forced MSI2 expression retards anagen entry and consequently, delays hair growth, while loss of Msi2 enhances hair regrowth. Further, our findings show that Msi2 maintains quiescent state of HFSCs in the process of telogen-to-anagen transition. At the molecular level, our unbiased transcriptome profiling shows that Msi2 represses Hh signaling activity and that Shh is its direct target in the HF. Taken together, our findings reveal the importance of Msi2 in suppressing hair regeneration and maintaining HFSC quiescence. Previously unreported Msi2-Shh-Gli1 pathway adds to the growing understanding of the complex network governing cyclic hair growth.

 

[Rofler]

Hair follicles’ transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog

I am not good at science. Is it about hair cell culturing?

https://www.researchgate.net/public..._directly_repressing_the_Hh_signaling_pathway

What does that study mean?

 

[InBeforeTheCure]

I am not good at science. Is it about hair cell culturing?

Nope. As the hair follicle transitions from telogen (the resting phase of the hair cycle) to anagen (the growth phase of the hair cycle), signals from the dermal papilla induce nearby secondary germ cells to proliferate rapidly, and these rapidly proliferating cells are called transit amplifying cells (TACs), which after several divisions differentiate into hair follicle matrix cells. TACs and matrix cells secrete Sonic Hedgehog (Shh), which activates stem cells in the bulge, and these stem cells migrate down and form the outer root sheath (ORS). As the hair cycle progresses, the bulge gets farther and farther away from the TACs/matrix, and after mid-anagen stem cell activation ceases as the bulge is too far away for Shh to reach it.

As the hair follicle grows during anagen, it expands downward. What this study shows is that Shh from the same TACs responsible for hair follicle stem cell activation also induce nearby precursors to adipocytes (fat cells) to proliferate. This makes the surrounding tissue fatter/thicker, which makes room for the hair follicle to grow into.

 

[Gone]

Do you think that's the same mechanism Cotsarelis referred to when he announced myfibroblasts could become adipocytes as a result of hair growth? I was reading more about that today, and their conclusion was that, most specifically, it was BMP that caused the myofibrolast transformation into adipocytes.

 

[InBeforeTheCure]

Do you think that's the same mechanism Cotsarelis referred to when he announced myfibroblasts could become adipocytes as a result of hair growth? I was reading more about that today, and their conclusion was that, most specifically, it was BMP that caused the myofibrolast transformation into adipocytes.

Yeah, that's a different mechanism I guess.

 

[InBeforeTheCure]

@Swoop

https://www.researchgate.net/public..._directly_repressing_the_Hh_signaling_pathway

I was just going through the data from the Hagenaars et al. GWAS and noticed there were two SNPs - rs62060349 (p = 3.51e-22) and rs145226407 (p = 4.83e-14) -- associated with A.G.A near MSI2.

So it's possible that the mechanism described in that study could play some part in A.G.A.