Niche-specific factors dynamically regulate sebaceous gland stem cells during skin homeostasis and aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE125737 | GEO | 2019/08/20
REPOSITORIES: GEO
Similar Datasets
Project description:Oil-secreting sebaceous glands (SGs) are critical for proper skin function; however, it remains unclear how different factors act together to modulate SG stem cells. Here, we provide functional evidence that each SG lobe is serviced by its own dedicated stem cell population. Upon ablating Notch signaling in different skin subcompartments, we find that this pathway exerts dual counteracting effects on SGs. Suppressing Notch in SG progenitors traps them in a hybrid state where stem and differentiation features become intermingled. In contrast, ablating Notch outside of the SG stem cell compartment indirectly drives SG expansion. Finally, we report that a K14:K5→K14:K79 keratin shift occurs during SG differentiation. Deleting K79 destabilizes K14 in sebocytes, and attenuates SGs and eyelid meibomian glands, leading to corneal ulceration. Altogether, our findings demonstrate that SGs integrate diverse signals from different niches and suggest that mutations incurred within one stem cell compartment can indirectly influence another.
| S-EPMC6832854 | biostudies-literature
Project description:Niche-specific factors dynamically regulate sebaceous gland stem cells during skin homeostasis and aging
| PRJNA517423 | ENA
Project description:p53 is an important inducer of organismal aging. However, its roles in the aging of skin remain unclear. Here we show that mice with chronic activation of p53 develop an aging phenotype in the skin associated with a reduction of subcutaneous fat and loss of sebaceous gland (SG). The reduction in the fat layer may result from the decrease of mammalian TOR complex 1 (mTORC1) activity accompanied by elevated expression of energy expenditure genes, and possibly as compensatory effects, leading to the elevation of peroxisome proliferator-activated receptor (PPAR)?, an inducer of sebocyte differentiation. In addition, Blimp1(+) sebocytes become depleted concomitantly with an increase in cellular senescence, which can be reversed by PPAR? antagonist (BADGE) treatment. Therefore, our results indicate that p53-mediated aging of the skin involves not only thinning through the loss of subdermal fat, but also xerosis or drying of the skin through declining sebaceous gland activity.
| S-EPMC3973209 | biostudies-literature
Project description:Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous epithelial-mesenchymal interactions. Once the first HF cycle is complete it repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans are found on the cell surface and in the extracellular matrix where they influence a variety of biological processes by interacting with physiologically important proteins, such as growth factors. Inhibition of heparanase (an HS endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like process. Therefore, this study aimed to elucidate the precise role of HS in HF morphogenesis and cycling. An inducible tetratransgenic mouse model was generated to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from P21. Interestingly, EXT1(StEpiΔ/StEpiΔ) mice presented solely anagen HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair regrowth in the EXT1(StEpiΔ/StEpiΔ) mice and hindered cycling into catagen. The ablation of HS in the interfollicular epidermal cells of mature skin led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic Hedgehog signaling pathway regulates HF formation during embryogenesis and prevents HF formation in mature skin. Finally, the knock-out of HS also led to the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature mice, leading to exacerbated sebum production and accumulation on the skin surface. Therefore, our findings clearly show that an intricate control of HS levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF cycling.
| S-EPMC4155684 | biostudies-literature
Project description:The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain poorly characterized at the molecular level. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of HFSC located outside the bulge. When applied to the bulk of HFSC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge HFSC regulators. Among the latter, we found that PRDM16 was preferentially expressed within the Junctional Zone (JZ). To investigate PRDM16 function within the JZ SCs, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, although these K14-Cre-Prdm16fl/fl mice did not show any major skin or hair abnormalities, the homeostasis of the SG was clearly compromised. Namely, PRDM16 deficient mice displayed enlarged SGs and excessive sebum production, thus resembling some of the features associated with certain human conditions (i.e. acne, sebaceous hyperplasia). Overall, our study provides a list of putative novel regulators of HFSC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis.
2021-03-26 | GSE169647 | GEO
Project description:The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain poorly characterized at the molecular level. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of HFSC located outside the bulge. When applied to the bulk of HFSC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge HFSC regulators. Among the latter, we found that PRDM16 was preferentially expressed within the Junctional Zone (JZ). To investigate PRDM16 function within the JZ SCs, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, although these K14-Cre-Prdm16fl/fl mice did not show any major skin or hair abnormalities, the homeostasis of the SG was clearly compromised. Namely, PRDM16 deficient mice displayed enlarged SGs and excessive sebum production, thus resembling some of the features associated with certain human conditions (i.e. acne, sebaceous hyperplasia). Overall, our study provides a list of putative novel regulators of HFSC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis.
2021-03-26 | GSE169648 | GEO
Project description:Laser capture microdissection enriched for sebaceous gland basal cells at P4, P10, P30
2019-07-15 | GSE126491 | GEO
Project description:B-lymphocyte-induced nuclear maturation protein 1 (BLIMP1) was previously reported to define a sebaceous gland (SG) progenitor population in the epidermis. However, the recent identification of multiple stem cell populations in the hair follicle junctional zone has led us to re-evaluate its function. We show, in agreement with previous studies, that BLIMP1 is expressed by postmitotic, terminally differentiated epidermal cells within the SG, interfollicular epidermis, and hair follicle. Epidermal overexpression of c-Myc results in loss of BLIMP1(+) cells, an effect modulated by androgen signaling. Epidermal-specific deletion of Blimp1 causes multiple differentiation defects in the epidermis in addition to SG enlargement. In culture, BLIMP1(+) sebocytes have no greater clonogenic potential than BLIMP1(-) sebocytes. Finally, lineage-tracing experiments reveal that, under steady-state conditions, BLIMP1-expressing cells do not divide. Thus, rather than defining a sebocyte progenitor population, BLIMP1 functions in terminally differentiated cells to maintain homeostasis in multiple epidermal compartments.
| S-EPMC4223714 | biostudies-literature
Project description:Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.
| S-EPMC5951834 | biostudies-literature
Project description:Due to limited model systems for sebaceous glands we investigated potential suitability of preputial glands as model for sebaceous glands. We performed single-cell sequencing of murine preputial glands and back skin biopsies. This study revealed striking differences in lipid metabolizing enzyme expression and differentiation pathways found in sebocytes of the different tissues.
2022-01-24 | GSE185268 | GEO