Modulatory Role of Sensory Innervation on Hair Follicle Stem Cell Progeny during Wound Healing of the Rat Skin

ABSTRACT Stem cell differentiation is accompanied by increased mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine and spermine, which are essential for cell growth and stem cell maintenance. However, the role of polyamines as endogenous effectors of stem cell fate and whether they act through translational control remains obscure. Here, we investigate the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. Compared to progenitor cells, HFSCs showed lower translation rates, correlating with reduced polyamine levels. Surprisingly, overall polyamine depletion decreased translation but did not affect cell fate. In contrast, specific depletion of natural polyamines mediated by spermidine/spermine N1-acetyltransferase (SSAT; also known as SAT1) activation did not reduce translation but enhanced stemness. These results suggest a translation-independent role of polyamines in cell fate regulation. Indeed, we identified N1-acetylspermidine as a determinant of cell fate that acted through increasing self-renewal, and observed elevated N1-acetylspermidine levels upon depilation-mediated HFSC proliferation and differentiation in vivo. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions. This article has an associated First Person interview with the first author of the paper.

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A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle

10.1101/230771 ◽

2017 ◽

Author(s):

María I. Calvo-Sánchez ◽

Elisa Carrasco ◽

Sandra Fernández-Martos ◽

Gema Moreno ◽

Carmelo Bernabeu ◽

...

Keyword(s):

Stem Cell ◽

Hair Follicle ◽

Major Question ◽

Hair Follicle Stem Cell ◽

Biological Oscillator ◽

Sequential Activation ◽

Bmp Signalling ◽

Stem Cell Populations ◽

Stem Cell Niches

ABSTRACTThe hair follicle is a biological oscillator that alternates growth, regression and rest phases driven by the sequential activation of the proliferation/differentiation programs of resident stem cell populations. The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling, while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity. A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways. Here we have focused on the role of Endoglin (Eng), a key coreceptor for members of the Tgf-β/Bmp family of growth factors.Using an Eng haploinsufficient mouse model we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell niches. We further report that β-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that β-catenin interacts with Smad4 in a Bmp/Eng dependent context and both proteins act synergistically to activate Eng promoter transcription. These observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback crosstalk between Wnt/β-catenin and Bmp/Smad signals.

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