Abstract

Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling.

Highlights

  • Hair follicles undergo cyclic bouts of growth, regression and rest throughout life in mammalians [1,2,3]

  • Foxp1 is relocated from nucleus to cytoplasm in Hair follicle stem cells (HFSCs) from anagen to catagen accompanying the rise of Reactive oxygen species (ROS) levels

  • The specificity of our self-made Foxp1 antibody was tested by IgG control in S1A Fig. The expression of Foxp1 in HFSCs was evidenced by co-localization with NFATc1 (S1B Fig)

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Summary

Introduction

Hair follicles undergo cyclic bouts of growth (anagen), regression (catagen) and rest (telogen) throughout life in mammalians [1,2,3]. Hair follicle stem cells (HFSCs) in the bulge niches are responsible for regeneration of various hair follicle cell lineages within well-defined anatomical compartments[4]. HFSCs and their close progenies, hair germ (HG) cells, are activated by dermal papilla (DP), a cluster of underlying mesenchymal cells[5]. HFSCs develop into the upper half of the slow-amplifying outer root sheath (ORS) and into the lower half of the fast-cycling ORS[6]. Matrix cells (Mx) at the base of the hair follicle divide rapidly but transiently prior to migrating upwards to form the hair sheath.

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