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GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing.

Zhao H, Qiao J, Zhang S, Zhang H, Lei X, Wang X, Deng Z, Ning L, Cao Y, Guo Y, Liu S, Duan E - Sci Rep (2015)

Bottom Line: Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1.Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage.The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.

ABSTRACT
G protein-coupled receptors (GPCRs) mediate multiple key biological processes in the body. The orphan receptor GPR39 has been reported to be involved in various pathophysiological events. However, the function of GPR39 in skin biology remains unknown. Using a genetically engineered mouse strain in which lacZ expression faithfully replaced endogenous Gpr39 expression, we discovered a unique expression pattern of Gpr39 in the sebaceous gland (SG). Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1. Further investigations showed that GPR39 was spatiotemporally expressed during skin wound repair. Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage. The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

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Localisation of GPR39 protein expression in HFs.(a) Immunostaining of GPR39 (green) in the HF and SG. PI was used for counterstaining (red). (b) Costaining of GPR39 (red) and Blimp1 (green) in the HF. Hoechst was used for counterstaining (blue). Inserted in the panel are separate colour channels and an enlarged picture of the SG section. (c) Costaining of GPR39 (red) and Lrig1 (green) in the HF. (d) SGs detached from the tail skin after dispase digestion. (e) Immunostaining of GPR39 in detached SGs. PI was used for counter staining (red). (f) Costaining of GPR39 (red) and Blimp1 (green) in a detached SG. The cells were counterstained with Hoechst (blue). (g) Flow cytometric analysis of epidermal cells using a PE-conjugated GPR39 antibody. The upper panel shows cells stained with the GPR39 antibody, and the lower panel shows the negative control without antibody staining. Inserted in the upper panel is an image of a sorted cell with PE fluorescence. (h) Expression of GPR39 in a human hair follicle. Arrows indicate positive signals. HF, hair follicle; SG, sebaceous gland; Epi, epidermis. Bar (a) = 25 μm, (b, c) = 20 μm, (d) = 5 μm, (e, f, g, h) = 20 μm.
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f2: Localisation of GPR39 protein expression in HFs.(a) Immunostaining of GPR39 (green) in the HF and SG. PI was used for counterstaining (red). (b) Costaining of GPR39 (red) and Blimp1 (green) in the HF. Hoechst was used for counterstaining (blue). Inserted in the panel are separate colour channels and an enlarged picture of the SG section. (c) Costaining of GPR39 (red) and Lrig1 (green) in the HF. (d) SGs detached from the tail skin after dispase digestion. (e) Immunostaining of GPR39 in detached SGs. PI was used for counter staining (red). (f) Costaining of GPR39 (red) and Blimp1 (green) in a detached SG. The cells were counterstained with Hoechst (blue). (g) Flow cytometric analysis of epidermal cells using a PE-conjugated GPR39 antibody. The upper panel shows cells stained with the GPR39 antibody, and the lower panel shows the negative control without antibody staining. Inserted in the upper panel is an image of a sorted cell with PE fluorescence. (h) Expression of GPR39 in a human hair follicle. Arrows indicate positive signals. HF, hair follicle; SG, sebaceous gland; Epi, epidermis. Bar (a) = 25 μm, (b, c) = 20 μm, (d) = 5 μm, (e, f, g, h) = 20 μm.

Mentions: GPR39 protein expression in wild-type mice was examined by immunofluorescence staining. As shown in Fig. 2a, the membrane location of GPR39 was clear in the cells at the SG opening, where unipotent Blimp1+ SG stem cells have been reported to reside9. To analyse the relationship between the GPR39+ cells and the Blimp1+ cells, we costained with these markers and found that GPR39 and Blimp1 largely marked the same cell population within the SG (Fig. 2b). GPR39 expression was also compared to the expression of the isthmus stem cell marker Lrig1. Whereas Lrig1 staining exhibited a typical isthmus distribution, GPR39+ cells were observed adjacent to Lrig1+ cells, with partial overlapping (Fig. 2c). After dispase digestion, we stained GPR39 and Blimp1 in detached SGs (Fig. 2d). These results also verified that GPR39 was expressed in small cells at the SG opening (Fig. 2e) and colocalised with Blimp1 (Fig. 2f). A flow cytometric analysis indicated that the GPR39+ cells accounted for approximately 0.05% of all epidermal cells (Fig. 2g). In human skin, GPR39 expression was also restricted to the opening of the SG (Fig. 2h). In summary, the cell-specific expression of GPR39 and its colocalisation with Blimp1 suggested that GPR39 may mark a population of putative SG stem cells.


GPR39 marks specific cells within the sebaceous gland and contributes to skin wound healing.

Zhao H, Qiao J, Zhang S, Zhang H, Lei X, Wang X, Deng Z, Ning L, Cao Y, Guo Y, Liu S, Duan E - Sci Rep (2015)

Localisation of GPR39 protein expression in HFs.(a) Immunostaining of GPR39 (green) in the HF and SG. PI was used for counterstaining (red). (b) Costaining of GPR39 (red) and Blimp1 (green) in the HF. Hoechst was used for counterstaining (blue). Inserted in the panel are separate colour channels and an enlarged picture of the SG section. (c) Costaining of GPR39 (red) and Lrig1 (green) in the HF. (d) SGs detached from the tail skin after dispase digestion. (e) Immunostaining of GPR39 in detached SGs. PI was used for counter staining (red). (f) Costaining of GPR39 (red) and Blimp1 (green) in a detached SG. The cells were counterstained with Hoechst (blue). (g) Flow cytometric analysis of epidermal cells using a PE-conjugated GPR39 antibody. The upper panel shows cells stained with the GPR39 antibody, and the lower panel shows the negative control without antibody staining. Inserted in the upper panel is an image of a sorted cell with PE fluorescence. (h) Expression of GPR39 in a human hair follicle. Arrows indicate positive signals. HF, hair follicle; SG, sebaceous gland; Epi, epidermis. Bar (a) = 25 μm, (b, c) = 20 μm, (d) = 5 μm, (e, f, g, h) = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4300488&req=5

f2: Localisation of GPR39 protein expression in HFs.(a) Immunostaining of GPR39 (green) in the HF and SG. PI was used for counterstaining (red). (b) Costaining of GPR39 (red) and Blimp1 (green) in the HF. Hoechst was used for counterstaining (blue). Inserted in the panel are separate colour channels and an enlarged picture of the SG section. (c) Costaining of GPR39 (red) and Lrig1 (green) in the HF. (d) SGs detached from the tail skin after dispase digestion. (e) Immunostaining of GPR39 in detached SGs. PI was used for counter staining (red). (f) Costaining of GPR39 (red) and Blimp1 (green) in a detached SG. The cells were counterstained with Hoechst (blue). (g) Flow cytometric analysis of epidermal cells using a PE-conjugated GPR39 antibody. The upper panel shows cells stained with the GPR39 antibody, and the lower panel shows the negative control without antibody staining. Inserted in the upper panel is an image of a sorted cell with PE fluorescence. (h) Expression of GPR39 in a human hair follicle. Arrows indicate positive signals. HF, hair follicle; SG, sebaceous gland; Epi, epidermis. Bar (a) = 25 μm, (b, c) = 20 μm, (d) = 5 μm, (e, f, g, h) = 20 μm.
Mentions: GPR39 protein expression in wild-type mice was examined by immunofluorescence staining. As shown in Fig. 2a, the membrane location of GPR39 was clear in the cells at the SG opening, where unipotent Blimp1+ SG stem cells have been reported to reside9. To analyse the relationship between the GPR39+ cells and the Blimp1+ cells, we costained with these markers and found that GPR39 and Blimp1 largely marked the same cell population within the SG (Fig. 2b). GPR39 expression was also compared to the expression of the isthmus stem cell marker Lrig1. Whereas Lrig1 staining exhibited a typical isthmus distribution, GPR39+ cells were observed adjacent to Lrig1+ cells, with partial overlapping (Fig. 2c). After dispase digestion, we stained GPR39 and Blimp1 in detached SGs (Fig. 2d). These results also verified that GPR39 was expressed in small cells at the SG opening (Fig. 2e) and colocalised with Blimp1 (Fig. 2f). A flow cytometric analysis indicated that the GPR39+ cells accounted for approximately 0.05% of all epidermal cells (Fig. 2g). In human skin, GPR39 expression was also restricted to the opening of the SG (Fig. 2h). In summary, the cell-specific expression of GPR39 and its colocalisation with Blimp1 suggested that GPR39 may mark a population of putative SG stem cells.

Bottom Line: Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1.Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage.The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

View Article: PubMed Central - PubMed

Affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.

ABSTRACT
G protein-coupled receptors (GPCRs) mediate multiple key biological processes in the body. The orphan receptor GPR39 has been reported to be involved in various pathophysiological events. However, the function of GPR39 in skin biology remains unknown. Using a genetically engineered mouse strain in which lacZ expression faithfully replaced endogenous Gpr39 expression, we discovered a unique expression pattern of Gpr39 in the sebaceous gland (SG). Using various methods, we confirmed that GPR39 marked a specific cell population at the opening of the SG and colocalised with the SG stem cell marker Blimp1. Further investigations showed that GPR39 was spatiotemporally expressed during skin wound repair. Although it was dispensable for skin development and homeostasis, GPR39 contributed positively to skin wound healing: its loss led to a delay in wound healing during the intermediate stage. The present study reveals a novel role of GPR39 in both dermatology and stem cell biology that has not been previously recognised.

Show MeSH
Related in: MedlinePlus