Integration of transcriptomics and spatial biology analyses reveals Galactomyces ferment filtrate promotes epidermal interconnectivity via induction of keratinocyte differentiation, proliferation and cellular bioenergetics

IF 2.7 4区 医学 Q2 DERMATOLOGY
John M. Snowball, Bradley B. Jarrold, Yvonne DeAngelis, Chuiying Li, Holly A. Rovito, Michelle C. Hare, Timothy Laughlin, Anna L. Evdokiou, John E. Oblong
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Abstract

Objective

Human skin is the first line of defence from environmental factors such as solar radiation and is susceptible to premature ageing, including a disruption in epidermal differentiation and homeostasis. We evaluated the impact of a Galactomyces Ferment Filtrate (GFF) on epidermal differentiation and response to oxidative stress.

Methods

We used transcriptomics, both spatial and traditional, to assess the impact of GFF on epidermal biology and homeostasis in keratinocytes (primary or immortalized) and in ex vivo skin explant tissue. The effect of GFF on cell adhesion rates, cellular ATP levels and proliferation rates were quantitated. Oxidative phosphorylation and glycolytic rates were measured under normal and stress-induced conditions.

Results

Transcriptomics from keratinocytes and ex vivo skin explants from multiple donors show GFF induces keratinocyte differentiation, skin barrier development and cell adhesion while simultaneously repressing cellular stress and inflammatory related processes. Spatial transcriptomics profiling of ex vivo skin indicated basal keratinocytes at the epidermal-dermal junction and cornifying keratinocytes in the top layer of the epidermis as the primary cell types influenced by GFF treatment. Additionally, GFF significantly increases crosstalk between suprabasal and basal keratinocytes. To support these findings, we show that GFF can significantly increase cell adhesion and proliferation in keratinocytes. GFF also protected overall cellular bioenergetics under metabolic or oxidative stress conditions.

Conclusion

Our findings provide novel insights into cellular differences and epidermal spatial localization in response to GFF, supporting previous findings that this filtrate has a significant impact on epidermal biology and homeostasis, particularly on spatially defined crosstalk. We propose that GFF can help maintain epidermal health by enhancing keratinocyte crosstalk and differentiation/proliferation balance as well as promoting an enhanced response to stress.

Abstract Image

整合转录组学和空间生物学分析表明,半乳酵母菌发酵滤液可通过诱导角质细胞分化、增殖和细胞生物能促进表皮的相互连接。
目的:人体皮肤是抵御太阳辐射等环境因素的第一道防线,容易过早衰老,包括表皮分化和平衡紊乱。我们评估了半乳酵母菌发酵滤液(GFF)对表皮分化和氧化应激反应的影响:我们使用转录组学(包括空间和传统转录组学)来评估 GFF 对角质形成细胞(原代或永生化)和体外皮肤组织中表皮生物学和稳态的影响。量化了 GFF 对细胞粘附率、细胞 ATP 水平和增殖率的影响。在正常和应激诱导条件下测量了氧化磷酸化和糖酵解率:来自多个供体的角朊细胞和体外皮肤外植体的转录组学显示,GFF能诱导角朊细胞分化、皮肤屏障发育和细胞粘附,同时抑制细胞应激和炎症相关过程。体外皮肤的空间转录组学分析表明,表皮-真皮交界处的基底角质细胞和表皮顶层的粟粒化角质细胞是受 GFF 处理影响的主要细胞类型。此外,GFF 还能明显增加基底层和上层角质形成细胞之间的串联。为了支持这些发现,我们证明了 GFF 能显著增加角质形成细胞的细胞粘附和增殖。在新陈代谢或氧化应激条件下,GFF还能保护细胞的整体生物能:我们的研究结果为细胞差异和表皮空间定位对 GFF 的反应提供了新的见解,支持了之前的研究结果,即这种滤液对表皮生物学和平衡有重大影响,特别是对空间定义的串联。我们认为,GFF 可通过加强角质细胞的串联和分化/增殖平衡以及促进对压力的更强反应来帮助维持表皮健康。
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来源期刊
CiteScore
4.60
自引率
4.30%
发文量
73
期刊介绍: The Journal publishes original refereed papers, review papers and correspondence in the fields of cosmetic research. It is read by practising cosmetic scientists and dermatologists, as well as specialists in more diverse disciplines that are developing new products which contact the skin, hair, nails or mucous membranes. The aim of the Journal is to present current scientific research, both pure and applied, in: cosmetics, toiletries, perfumery and allied fields. Areas that are of particular interest include: studies in skin physiology and interactions with cosmetic ingredients, innovation in claim substantiation methods (in silico, in vitro, ex vivo, in vivo), human and in vitro safety testing of cosmetic ingredients and products, physical chemistry and technology of emulsion and dispersed systems, theory and application of surfactants, new developments in olfactive research, aerosol technology and selected aspects of analytical chemistry.
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