Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury

Veniaminova, Natalia A.; Jia, Yunlong Y.; Hartigan, Adrien M.; Huyge, Thomas J.; Tsai, Shih-Ying; Grachtchouk, Marina; Nakagawa, Seitaro; Dlugosz, Andrzej A.; Atwood, Scott X.; Wong, Sunny Y.

doi:10.1016/j.celrep.2023.113121

Cited by 20 publications

(13 citation statements)

References 91 publications

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“…We noticed that the AR-expressing cell population could be divided into two groups: a basal stem cell population that co-expressed Lrig1, but did not express FASN (arrow heads in Figure 4a,c), and an early differentiating sebocyte population that expressed FASN, but did not express Lrig1 (arrows in Figure 4a,c). We hypothesize that the Lrig1+/AR+ population is a progenitor cell population, in addition to the Lrig1+ stem cells, similar to the recently identified transitional basal cell population in the SG (Veniaminova et al, 2023). There were no significant differences in the number of Lrig1 positive stem cells per SG, or the AR-expressing progenitor population between treatments at 3 days post treatment (Figure 4d,e).…”

Section: Notch Activity In the Sg Stem Cells Is Required To Prevent U...supporting

confidence: 68%

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

Abidi,

Chan,

Seidel

et al. 2024

Preprint

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The sebaceous gland (SG) is a vital appendage of the epidermis, and its normal homeostasis and function is crucial for effective maintenance of the skin barrier. Notch signaling is a well-known regulator of epidermal differentiation, and has also been shown to be involved in postnatal maintenance of SGs. However, the precise role of Notch signaling in regulating SG differentiation in the adult homeostatic skin remains unclear. While there is evidence to suggest that Notch1 is the primary Notch receptor involved in regulating the differentiation process, the ligand remains unknown. Using monoclonal therapeutic antibodies designed to specifically inhibit of each of the Notch ligands or receptors, we have identified the Jag2/Notch1 signaling axis as the primary regulator of sebocyte differentiation in homeostatic skin. Mature sebocytes are lost upon specific inhibition of the Jag2 ligand or Notch1 receptor, resulting in the accumulation of proliferative stem/progenitor cells in the SG. Most strikingly, this phenotype is reversible, as these stem/progenitor cells re-enter differentiation when the inhibition of Notch activity is lifted. Thus, Notch activity promotes correct sebocyte differentiation, and is required to restrict progenitor proliferation.

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Section: Notch Activity In the Sg Stem Cells Is Required To Prevent U...supporting

confidence: 68%

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

Abidi,

Chan,

Seidel

et al. 2024

Preprint

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“…In addition, the WNT/β-catenin pathway can also promote the recruitment of HFSCs and fill SGs. SG cells and HFSCs filled with SGs can further differentiate into sebaceous cells [89,90]. These biological behaviors play a positive stimulating, and thus contributory, role in wound repair.…”

Section: Wnt Signals In Hfscsmentioning

confidence: 97%

The Roles of WNT Signaling Pathways in Skin Development and Mechanical-Stretch-Induced Skin Regeneration

Bai,

Guo,

Liu

et al. 2023

Biomolecules

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The WNT signaling pathway plays a critical role in a variety of biological processes, including development, adult tissue homeostasis maintenance, and stem cell regulation. Variations in skin conditions can influence the expression of the WNT signaling pathway. In light of the above, a deeper understanding of the specific mechanisms of the WNT signaling pathway in different physiological and pathological states of the skin holds the potential to significantly advance clinical treatments of skin-related diseases. In this review, we present a comprehensive analysis of the molecular and cellular mechanisms of the WNT signaling pathway in skin development, wound healing, and mechanical stretching. Our review sheds new light on the crucial role of the WNT signaling pathway in the regulation of skin physiology and pathology.

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“…SG expresses all PPAR isoforms. However, PPARγ seems to be a crucial and necessary requirement for SG genesis and homeostasis [ 60 , 61 , 62 , 63 ]. Mice with a targeted deletion of PPARγ show the dramatic downregulation of transcripts encoding for genes related to gland development and sebum production, leading to an asebia phenotype.…”

Section: Pparγ and The Sebaceous Glandmentioning

confidence: 99%

New Insights into the Role of PPARγ in Skin Physiopathology

Briganti,

Mosca,

Di Nardo

et al. 2024

Biomolecules

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Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.

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Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury

Cited by 20 publications

References 91 publications

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation

The Roles of WNT Signaling Pathways in Skin Development and Mechanical-Stretch-Induced Skin Regeneration

New Insights into the Role of PPARγ in Skin Physiopathology

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