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PLoS Biol. 2018 Mar 28;16(3):e2002864. doi: 10.1371/journal.pbio.2002864. eCollection 2018 Mar.

Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture.

Author information

1
Department of Drug Discovery and Development, Laboratory of Molecular Medicine, Fondazione Istituto Italiano di Tecnologia (IIT), Genoa, Italy.
2
The Centre for Dermatology Research, University of Manchester, MAHSC, and National Institutes of Health Biomedical Research Center, Manchester, United Kingdom.
3
Monasterium Laboratory, Münster, Germany.
4
Department of Dermatology, University of Münster, Münster, Germany.
5
Department of Dermatology and Cutaneous Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

Abstract

Autophagy plays a crucial role in health and disease, regulating central cellular processes such as adaptive stress responses, differentiation, tissue development, and homeostasis. However, the role of autophagy in human physiology is poorly understood, highlighting a need for a model human organ system to assess the efficacy and safety of strategies to therapeutically modulate autophagy. As a complete, cyclically remodelled (mini-)organ, the organ culture of human scalp hair follicles (HFs), which, after massive growth (anagen), spontaneously enter into an apoptosis-driven organ involution (catagen) process, may provide such a model. Here, we reveal that in anagen, hair matrix keratinocytes (MKs) of organ-cultured HFs exhibit an active autophagic flux, as documented by evaluation of endogenous lipidated Light Chain 3B (LC3B) and sequestosome 1 (SQSTM1/p62) proteins and the ultrastructural visualization of autophagosomes at all stages of the autophagy process. This autophagic flux is altered during catagen, and genetic inhibition of autophagy promotes catagen development. Conversely, an anti-hair loss product markedly enhances intrafollicular autophagy, leading to anagen prolongation. Collectively, our data reveal a novel role of autophagy in human hair growth. Moreover, we show that organ-cultured scalp HFs are an excellent preclinical research model for exploring the role of autophagy in human tissue physiology and for evaluating the efficacy and tissue toxicity of candidate autophagy-modulatory agents in a living human (mini-)organ.

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