Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro

Alona Feldman,Yahav Yosefzon,Elle Koren,Tomer Shlomi,Egor Sedov,Yaron Fuchs,Dzmitry Mukha,Itzhak I Maor

doi:10.1038/s41467-019-10261-6

Alona Feldman, Yahav Yosefzon + Show 6 more

Open Access

https://doi.org/10.1038/s41467-019-10261-6

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Abstract

Most studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG). The SG has been proposed to be replenished by different pools of hair follicle stem cells and cells that resides in the SG base, marked by Blimp1. Here, we demonstrate that single Blimp1+ cells isolated from mice have the potential to generate SG organoids in vitro. Mimicking SG homeostasis, the outer layer of these organoids is composed of proliferating cells that migrate inward, undergo terminal differentiation and generating lipid-filled sebocytes. Performing confocal microscopy and mass-spectrometry, we report that these organoids exhibit known markers and a lipidomic profile similar to SGs in vivo. Furthermore, we identify a role for c-Myc in sebocyte proliferation and differentiation, and determine that SG organoids can serve as a platform for studying initial stages of acne vulgaris, making this a useful platform to identify potential therapeutic targets.

Highlights

Most studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG)
We identify a role for c-Myc in sebocyte proliferation and differentiation, and determine that SG organoids can serve as a platform for studying initial stages of acne vulgaris, making this a useful platform to identify potential therapeutic targets
We examined whether embedding cells in a basement membranelike extracellular 3D environment such as Matrigel, which has been successfully utilized in several epithelial stem cell platforms, could enable establishment of SG organoids (Fig. 1d)[12,13,14]

Summary

Introduction

Most studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG). One of the most widespread dermatological conditions, acne vulgaris, involves multiple factors including dysregulation of the SGs2 The pathogenesis of this disease includes hyperactivation of SGs, excessive keratin deposition and an increase in SG size, which is dependent upon sebocyte hyperproliferation and sebum production. It has recently been suggested that Blimp[1] functions in terminally differentiated sebocytes[8] as well as in granular IFE cells[9, 10] These reports prompted us to examine whether Blimp1+ cells cultured in the proper conditions have the capacity to replenish, as well as potentially generate, SG in vitro. We show that Blimp1+ cells isolated from adult mice have the potential to generate SG organoids that recapitulate the features of SGs in vivo. Here we describe a system that can be employed to study the biology of the SG along with a drug screening platform for SG pathologies

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