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

Chiara Parodi, Jonathan A Hardman, Giulia Allavena, Roberto Marotta, Tiziano Catelani, Marta Bertolini, Ralf Paus and Benedetto Grimaldi

PLOS Biology, 2018, vol. 16, issue 3, 1-22

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.Author summary: Human scalp hair follicles (HFs) experience a massive growth for years, until they spontaneously enter into a rapid, apoptosis-driven organ involution process, orchestrated by an organ-intrinsic “hair cycle clock,” the molecular control of which remains unclear. Human HFs maintain in vivo–like characteristics, even after being removed from the body, and spontaneously run through a fundamental organ-remodelling process, traversing through a stage of growth (anagen) and destruction (catagen) as a (mini-)organ model. Here, we exploit this unique remodelling (mini-)organ to unveil a crucial new role of autophagy in the growth of human HFs. We show that hair matrix keratinocytes exhibit an active autophagic flux ex vivo during anagen, which is altered after the transition to catagen. We find that genetic inhibition of follicular autophagy induces premature catagen and enhances hair matrix keratinocyte apoptosis, suggesting that autophagic flux in the anagen hair matrix is important for the maintenance of this stage. Indeed, we find that the principal ingredients of a product used to treat hair loss induces autophagy in organ-cultured human scalp HFs and promotes anagen. We conclude that organ-cultured human HFs are a suitable (mini-)organ system to study both the role of autophagy in human physiology ex vivo and to test candidate agents that modulate autophagy under clinically relevant conditions.

Date: 2018
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002864 (text/html)
https://journals.plos.org/plosbiology/article/file ... 02864&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pbio00:2002864

DOI: 10.1371/journal.pbio.2002864

Access Statistics for this article

More articles in PLOS Biology from Public Library of Science
Bibliographic data for series maintained by plosbiology ().