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Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
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Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Kandyba E, Leung Y, Chen YB, Widelitz R, Chuong CM, Kobielak K.
Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University
Abstract
Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signaling in the stem cells. We visualize the behavior of these modified stem cells, evaluating their hair-regenerating ability and profile their molecular expression. Bone morphogenetic protein (BMP)-inactivated stem cells exhibit molecular profiles resembling those of hair germs, yet still possess multipotentiality in vivo. These cells also exhibit up-regulation of Wnt7a, Wnt7b, and Wnt16 ligands and Frizzled (Fzd) 10 receptor. We demonstrate direct transcriptional modulation of the Wnt7a promoter. These results highlight a previously unknown intra-stem cell antagonistic competition, between BMP and Wnt signaling, to balance stem cell activity. Reduced BMP signaling and increased Wnt signaling tilts each stem cell toward a hair germ fate and, vice versa, based on a continuous scale dependent on the ratio of BMP/Wnt activity. This work reveals one more hierarchical layer regulating stem cell homeostasis beneath the stem cell-dermal papilla-based epithelial-mesenchymal interaction layer and the hair follicle-intradermal adipocyte-based tissue interaction layer. Although hierarchical layers are all based on BMP/Wnt signaling, the multilayered control ensures that all information is taken into consideration and allows hair stem cells to sum up the total activators/inhibitors involved in making the decision of activation.
Kandyba E, Leung Y, Chen YB, Widelitz R, Chuong CM, Kobielak K.
Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University
Abstract
Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signaling in the stem cells. We visualize the behavior of these modified stem cells, evaluating their hair-regenerating ability and profile their molecular expression. Bone morphogenetic protein (BMP)-inactivated stem cells exhibit molecular profiles resembling those of hair germs, yet still possess multipotentiality in vivo. These cells also exhibit up-regulation of Wnt7a, Wnt7b, and Wnt16 ligands and Frizzled (Fzd) 10 receptor. We demonstrate direct transcriptional modulation of the Wnt7a promoter. These results highlight a previously unknown intra-stem cell antagonistic competition, between BMP and Wnt signaling, to balance stem cell activity. Reduced BMP signaling and increased Wnt signaling tilts each stem cell toward a hair germ fate and, vice versa, based on a continuous scale dependent on the ratio of BMP/Wnt activity. This work reveals one more hierarchical layer regulating stem cell homeostasis beneath the stem cell-dermal papilla-based epithelial-mesenchymal interaction layer and the hair follicle-intradermal adipocyte-based tissue interaction layer. Although hierarchical layers are all based on BMP/Wnt signaling, the multilayered control ensures that all information is taken into consideration and allows hair stem cells to sum up the total activators/inhibitors involved in making the decision of activation.
CF- Posts : 514
Join date : 2011-06-19
Re: Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Wnt signalling is incrediblyimportant to all of this. Good post, CF. This aspect of the process is probably the one I'm least familiar with but on some other forums there are some great threads by guys like ganster/boldy on the role of wnt signalling. I believe CS has some posts concerning this as well.
AS54- Posts : 2367
Join date : 2011-08-12
Age : 35
Location : MI
Re: Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Thanks anthony. I was looking for something to increase WNT naturally but have not found anything other than the study about the Aconiti Ciliare Tuber extract where there's a table inside the publication with other natural substances that increase WNT, but I can't really afford to pay the 35 bucks to access it at the moment. However in my prior post it says TGF-β2 antagonizes BNP. And TGF-β2 is upregulated by 1α,25-dihydroxyvitamin D3 and all trans retinoic acid.
CF- Posts : 514
Join date : 2011-06-19
Re: Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Yes, A and D have important signalling functions, and wasn't even aware of their relationship with wnt, only that they regulate the androgen response. Man this is turning into an interesting post. I like posts like these that kind of turn into spring boards for more research.
AS54- Posts : 2367
Join date : 2011-08-12
Age : 35
Location : MI
Re: Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Wish I was smarter so I could understand these studies better :/
So D3 and Vit A are good in this scenario ya?
CF wrote:However in my prior post it says TGF-β2 antagonizes BNP. And TGF-β2 is upregulated by 1α,25-dihydroxyvitamin D3 and all trans retinoic acid.
So D3 and Vit A are good in this scenario ya?
theseeker86- Posts : 518
Join date : 2011-05-05
Re: Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation.
Yep, both A and D are good in this scenario.
CF- Posts : 514
Join date : 2011-06-19
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