Niche-Specific Factors Dynamically Regulate Sebaceous Gland Stem Cells in the Skin

Veniaminova, Natalia A.; Grachtchouk, Marina; Doane, Owen J.; Peterson, J.; Quigley, David A.; Lull, Madison V.; Pyrozhenko, Daryna V.; Nair, Raji R.; Patrick, Matthew; Balmain, Allan; Dlugosz, Andrzej A.; Tsoi, Lam C.; Wong, Sunny Y.

doi:10.1016/j.devcel.2019.08.015

Cited by 36 publications

(44 citation statements)

References 76 publications

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“…However, since markers such as SCA1 (Ly6a), that molecularly distinguish adult progenitors of the interfollicular epidermis from those of the upper outer root sheath were not yet expressed at this time, other differences in these signatures could represent early signs of their specification. Regarding the WNT lo populations, the Lhx2-expressing cells showed features more characteristic of early HF stem cells (Rhee et al, 2006), while the Krt79-expressing cells were likely to be early sebaceous gland progenitors (Veniaminova et al, 2019).…”

Section: Loss Of M6a Results In Perturbations Within the Single-cell mentioning

confidence: 99%

m6A RNA methylation impacts fate choices during skin morphogenesis

Carroll

Matos

et al. 2020

eLife

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N6-methyladenosine is the most prominent RNA modification in mammals. Here we study mouse skin embryogenesis to tackle m6A’s functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting with in vivo ribosomal profiling, we unearth a correlation between m6A-modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transcriptomics and bioinformatics, both signaling and canonical translation pathways show significant downregulation after m6A loss. Interestingly, however, many highly m6A-modified mRNAs are markedly upregulated upon m6A loss, and they encode RNA-methylation, RNA-processing and RNA-metabolism factors. Together, our findings suggest that m6A functions to enhance translation of key morphogenetic regulators, while also destabilizing sentinel mRNAs that are primed to activate rescue pathways when m6A levels drop.

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Section: Loss Of M6a Results In Perturbations Within the Single-cell mentioning

confidence: 99%

m6A RNA methylation impacts fate choices during skin morphogenesis

Carroll

Matos

et al. 2020

eLife

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“…Due to better mimic of the skin environment, some researchers reported that ASCs lifted to ALI showed a satisfactory differentiation [16]. Otherwise, differentiation of stem cells depends on the "niche," including diffusible paracrine effects, ECM, and cellular and mechanical factors [21,26,27,56], and most studies are based solely on 2D induction culture missing the biophysical microenvironments of the ECM. In contrast, 3D system using scaffolds (with interconnected pores) which mimic the structure and function of ECM proteins not only promotes cell adhesion, cell-biomaterial interactions, and cell proliferation [10,38,39], but also facilitates differentiation in skin regeneration [10,57,58].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, human ASCs (hASCs) have the advantages of wide sources, convenient access strategies, less damage to patients, rich stem cells in adipose tissue, and low immunogenicity [1,25], indicating that hASCs transdifferentiated into keratinocytes can be a promising strategy to promote wound healing. The differentiation of stem cells depends on the microenvironment of cell growth, named "niche" [21,26,27]. Currently, the main strategy for the differentiation of ASCs into keratinocytes is to add relevant inducing factors to the culture medium [22,23,28] or co-culture with target cells [29].…”

Section: Introductionmentioning

confidence: 99%

Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Gao

et al. 2020

Stem Cell Res Ther

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Background: Three-dimensional (3D) cultivation with biomaterials was proposed to facilitate stem cell epithelial differentiation for wound healing. However, whether human adipose-derived stem cells (hASCs) on collagen sponge scaffold (CSS) better differentiate to keratinocytes remains unclear. Methods: 3D cultivation with CSS on hASC epidermal differentiation co-cultured with HaCaT cells at air-liquid interface (ALI) was compared with two-dimensional (2D) form and cultivation without "co-culture" or "ALI." Cellular morphology, cell adhesion, and growth condition were evaluated, followed by the protein and gene expression of keratin 14 (K14, keratinocyte specific marker). Results: Typical cobblestone morphology of keratinocytes was remarkably observed in co-cultured hASCs at ALI, but those seeded on the CSS exhibited more keratinocyte-like cells under an invert microscope and scanning electron microscope. Desired cell adhesion and proliferation were confirmed in 3D differentiation groups by rhodamine-labeled phalloidin staining, consistent with H&E staining. Compared with those cultured in 2D culture system or without "ALI," immunofluorescence staining and gene expression analysis revealed hASCs co-cultured over CSS expressed K14 at higher levels at day 15. Conclusions: CSS is positive to promote epithelial differentiation of hASCs, which will foster a deeper understanding of artificial dermis in skin wound healing and regeneration.

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“…As postulated by the "comedone switch" hypothesis, comedones most likely arise because of abnormal differentiation of infundibular cells. [108,120] Recent studies, including the identification of Notch and keratin 79 as key players of infundibular differentiation and homeostasis in mouse hair follicles, [121] indicate that sebaceous gland lobes, serviced by own dedicated stem cell populations, are recipients of dual counteracting effects, which regulate the proliferation/differentiation equilibrium. Interestingly, the apparent initial step of comedogenesis, that is a perifollicular compartmentalization of skin-resident innate lymphoid cells as shown in the wild-type C57BL/6 mouse, is dependent on endocrine sebaceous gland factors.…”

Section: Folli Cul Ar D Ifferentiati On and Acnementioning

confidence: 99%

Endocrinology and immunology of acne: Two sides of the same coin

Zouboulis

2020

Experimental Dermatology

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Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

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Niche-Specific Factors Dynamically Regulate Sebaceous Gland Stem Cells in the Skin

Cited by 36 publications

References 76 publications

m6A RNA methylation impacts fate choices during skin morphogenesis

m6A RNA methylation impacts fate choices during skin morphogenesis

Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Endocrinology and immunology of acne: Two sides of the same coin

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