Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro

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

doi:10.1038/s41467-019-10261-6

Cited by 36 publications

(40 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 28 ] Triglycerides, a component of sebum lipids, may undergo hydrolysis by microbial lipases generating FFAs. [ 29‐31 ] Thus, next we compared the composition of the FFAs in the sebum surrounding back skin hairs of both WT and APOE −/− mice to assess whether the sebum of APOE −/− mice was affected by the hypercholesterolaemic profile of these mice. The sebum FFA composition of WT and APOE −/− mice was overall comparable (Figure 4D), indicating that the observed differential response to hypercholesterolaemia between back and ear skin cannot be explained by effects on the FFA content of sebum.…”

Section: Resultsmentioning

confidence: 99%

Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin

Cardoso

Absalah

Eck

et al. 2020

Experimental Dermatology

View full text Add to dashboard Cite

Experimental Dermatology. 2020;29:548-555. wileyonlinelibrary.com/journal/exd | INTRODUC TI ONOur understanding of skin morphology and lipid composition has benefitted greatly from the use of in vivo animal models. [1][2][3] In particular, mouse models have been proven a valuable tool in skin research as it offers the possibility to genetically manipulate these animals to study the role of specific skin components (eg enzymes, proteins, receptors) and to generate in vivo diseased skin models. [1,2] In research, the back skin and the ear skin of mice are commonly used sites. However, previous studies reported differential effects/ AbstractThe skin of the ear and the back are frequently selected sites in skin research using mouse models. However, distinct responses to treatment have been described between these two sites in several studies. Despite the crucial role of the stratum corneum (SC) in the skin barrier function of both dorsal back and ear skin, it remains unclear whether differences in lipid composition might underlie altered responses.Here, we compared the skin morphology and the barrier lipid composition of the ear with the back skin of wild-type mice. The ear contained more corneocyte layers in the SC and its barrier lipid composition was enriched with sphingosine ceramide subclasses, especially the short ones with a total chain length of 33-34 carbons. The free fatty acid (FFA) profile in the ear skin shifted towards shorter chains, significantly reducing the mean chain length to 23.3 vs 24.7 carbons in the back skin. In line, FFA species in the ear displayed a twofold increase in unsaturation index (P < .001). Gene expression in the ear skin revealed low expression of genes involved in lipid synthesis and uptake, indicating a reduced metabolic activity. Finally, the effects of hypercholesterolaemia on SC FFA composition was compared in ear and back skin of apolipoprotein E knockout (APOE −/− ) mice. Interestingly, the FFA profile in APOE −/− ear skin was minimally affected, while the FFA composition in the back skin was markedly changed in response to hypercholesterolaemia. In conclusion, ear and back skin have distinct barrier lipids and respond differently to elevated plasma cholesterol. K E Y W O R D S apolipoprotein E knockout mice, ceramides, fatty acids, wild-type mice | 549 MARTINS CARDOSO eT Al.phenotypes on ear skin vs the back skin regarding, among others, drug treatment (eg imiquimod-induced psoriasis, allergic contact dermatitis), melanocyte function and tissue regeneration. [4][5][6] The back skin comprises a relatively large area for performing experiments, but in hairy mice it contains a high density of hair follicles (fur) that can complicate the interpretation of the results. [5] In most studies, the fur is shaved to allow skin treatment and analysis. At the same time, the hair follicles may offer an alternative pathway for compound permeation. [7,8] In contrast, the ear represents an easily accessible, but small, skin area with a low density of hair follicles and centrally supported...

show abstract

Section: Resultsmentioning

confidence: 99%

Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin

Cardoso

Absalah

Eck

et al. 2020

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…[50,63] Therefore, CD44 expression in sebocytes at the surface of spheroids is likely to reflect a proliferative and undifferentiated state of SZ95 cells, which is similar to that of basal cells associated with SG in vivo. The establishment of SG spheroids by Yoshida et al [50] was, indeed, a landmark development in the recent years and was currently developed further by Feldman et al [64] and Boonekamp et al, [65] who constructed mouse . Examination of sections double-labelled with antibodies to K7 and cornifin confirmed that these markers were not co-expressed (D-F) (from: [47] under permission).…”

Section: D Sg -Lik E S Pheroidsmentioning

confidence: 99%

“…Furthermore, patient-specific 3D culture models and SKP may open new perspectives in understanding the genetic basis of skin diseases and in a therapeutic context in the field of personalized medicine. [50,64,80] In the future, such 3D systems could be combined with new scaffold technologies [98] and microfluidic platforms [99] allowing precise control and measurement of different culture parameters.…”

Section: Con Clus Ionmentioning

confidence: 99%

Sebaceous gland: Milestones of 30‐year modelling research dedicated to the “brain of the skin”

Zouboulis

Yoshida

et al. 2020

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…In contrast to other omics-technologies including genomics [8], transcriptomics [19] and proteomics [20] metabolomics is rarely used for characterization of organoid models. Whereas protocols for cell culture metabolomics are well established [21], only a few studies captured the metabolome from organoids by using NMR [22] and targeted [23] or non-targeted [24][25][26] LC-MS based profiling. In terms of non-targeted metabolomic profiling, there is an acute lack of optimization studies addressing problems such as the required sample amount and sampling conditions.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

et al. 2020

View full text Add to dashboard Cite

As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (<500 cells/injection) in the presence of an extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2′-deoxyuridine, 2′-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2′-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.

show abstract

Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro

Cited by 36 publications

References 49 publications

Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin

Barrier lipid composition and response to plasma lipids: A direct comparison of mouse dorsal back and ear skin

Sebaceous gland: Milestones of 30‐year modelling research dedicated to the “brain of the skin”

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

Contact Info

Product

Resources

About