毛根の生と死を司る化学物質(The chemical controlling life and death in hair follicles)

ad
ad
ad
ad
ad

ハゲをなくし、治癒を早める可能性のある発見 Discovery could help end baldness, speed healing

2022-07-25 カリフォルニア大学リバーサイド校(UCR)


Cross section of a typical hair follicle. (Qixuan Wang/UCR)

研究チームは、トランスフォーミング成長因子ベータ(TGF-β)というタンパク質が、幹細胞を含む毛包の細胞が分裂して新しい細胞を形成する過程、あるいは自らの死を指揮し、最終的に毛包全体を死に至らしめる過程をどのように制御しているかを明らかにしました。
TGF-βは2つの相反する役割を担っています。TGF-βは、毛包細胞の一部を活性化して新しい生命を生み出すのを助け、その後、細胞死のプロセスであるアポトーシスを指揮するのを助けます
多くの化学物質がそうであるように、違いを生むのはその量である。細胞が一定量のTGF-βを産生すれば、細胞分裂が活性化されます。多すぎるとアポトーシスを引き起こす。

<関連情報>

TGF-βによる毛包細胞の運命制御に関する確率的ブールモデル A probabilistic Boolean model on hair follicle cell fate regulation by TGF-β

Katherine Dinh,Qixuan Wang
Biophysical Journal  Published:June 16, 2022
DOI:https://doi.org/10.1016/j.bpj.2022.05.035

Abstract

Hair follicles (HFs) are mini skin organs that undergo cyclic growth. Various signals regulate HF cell fate decisions jointly. Recent experimental results suggest that transforming growth factor beta (TGF-β<?XML:NAMESPACE PREFIX = “[default] http://www.w3.org/1998/Math/MathML” NS = “http://www.w3.org/1998/Math/MathML” />β) exhibits a dual role in HF cell fate regulation that can be either anti- or pro-apoptosis. To understand the underlying mechanisms of HF cell fate control, we develop a novel probabilistic Boolean network (pBN) model on the HF epithelial cell gene regulation dynamics. First, the model is derived from literature, then refined using single-cell RNA sequencing data. Using the model, we both explore the mechanisms underlying HF cell fate decisions and make predictions that could potentially guide future experiments: 1) we propose that a threshold-like switch in the TGF-ββ strength may necessitate the dual roles of TGF-ββ in either activating apoptosis or cell proliferation, in cooperation with bone morphogenetic protein (BMP) and tumor necrosis factor (TNF) and at different stages of a follicle growth cycle; 2) our model shows concordance with the high-activator-low-inhibitor theory of anagen initiation; 3) we predict that TNF may be more effective in catagen initiation than TGF-ββ, and they may cooperate in a two-step fashion; 4) finally, predictions of gene knockout and overexpression reveal the roles in HF cell fate regulations of each gene. Attractor and motif analysis from the associated Boolean networks reveal the relations between the topological structure of the gene regulation network and the cell fate regulation mechanism. A discrete spatial model equipped with the pBN illustrates how TGF-ββ and TNF cooperate in initiating and driving the apoptosis wave during catagen.

タイトルとURLをコピーしました