I think BMP signalling is key Desmond...a piece of the puzzle, amongst other things
Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair.
Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair.
I don't know if you remember the post I made about the "first dermal signal". I have this gut feeling that the key to DP cell expansion lies within these signals! During embryogenesis the "first dermal signal" tells mesenchymal:epithelial cells that are in contact with each other to form DP cells! That's it! Unfortunately though, we only know less than a handful of these signals and most of them are unkown! The ones we know of are:
- BMP (activation)
- Wnt (inhibition & activation)
- FGF (inhibition)
- Vitamin D (promoter)
Dr Ohyama tested these signals and they significantly increased gene expression of cultured DP cells. This was only a year ago!
This is my 5 year plan:
First 2 years: Combine Ohyama's signals with Jahoda's 3D spheroid technique to master DP culturing expansion!
Next 3 years: Follow Tsuji's "Hair germ method" technology to generate human hair follicles by using these cultured DP cells and epithelial stem cells.
I'm seeing another Professor in Sydney on Wednesday to see if he's prepared to take me on! - Fingers crossed!
On a side note: guys imagine if we could have enough money to give researchers grants to conduct these studies. How awesome would that be?
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