The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse
Abstract Background Hair follicle stem cells (HFSC) play an essential role in the maintenance of hair homeostasis; during the hair cycle, HFSC remain quiescent for most of its duration. The hairpoor mouse (+ /Hr Hp ), an animal model of Marie-Unna hypotrichosis (MUHH), overexpresses hairless in the...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-02898-w |
| _version_ | 1811254275907518464 |
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| author | Keonwoo Choi Sang-Hee Park Seo-Yeon Park Sungjoo Kim Yoon |
| author_facet | Keonwoo Choi Sang-Hee Park Seo-Yeon Park Sungjoo Kim Yoon |
| author_sort | Keonwoo Choi |
| collection | DOAJ |
| description | Abstract Background Hair follicle stem cells (HFSC) play an essential role in the maintenance of hair homeostasis; during the hair cycle, HFSC remain quiescent for most of its duration. The hairpoor mouse (+ /Hr Hp ), an animal model of Marie-Unna hypotrichosis (MUHH), overexpresses hairless in the bulge, inner root sheath, and outer root sheath of HF and shows the same phenotype as in MUHH patients manifesting sparse hair with progression to alopecia with age. The aim of this study was to gain an understanding of the hair cycle and the status of HFSC during the hair cycle of the hairpoor mouse in order to delineate the pathogenesis of MUHH. Methods H&E staining was performed in order to define the state of the hair follicle. FACS analysis and immunostaining were performed at the 1st and 2nd telogen stages for observation of the HFSC. A label retaining assay was performed to determine the quiescent state of hair follicles. qRT-PCR was performed to determine expression of factors involved in niche signaling and Wnt signaling. Results We observed a drastic decrease in the number of hair follicles after the 1st telogen, followed by an intensified disturbance in the hair cycle with shorter anagen as well as 2nd telogen in the hairpoor mouse. A dramatic reduction in the number of CD34 expressing bulges as well as cells was observed at the telogen of the HFs, with prominent high proliferation of bulge cells, suggesting the loss of HFSC quiescence in the hairpoor mouse. The increased cell proliferation in HF was reiterated following the synchronization of the hair cycle, leading to acceleration of HF cycling. Reduced expression of Fgf18 and Bmp6, the factors involved in HFSC quiescence, was observed in the HFSC niche of the hairpoor mouse. In addition, disturbed expression of Wnt signaling molecules including Wnt7b, Wnt10b, and Sfrp1 was observed, which induced the telogen-to-anagen transition of HFs in the hairpoor mouse. Conclusions These results indicate that the quiescent state of HFSC is not properly maintained in the hairpoor mouse, consequently leading HFs to the completely disarrayed hair cycle. These findings may provide an understanding of an underlying mechanism for development of alopecia with age in MUHH patients. |
| first_indexed | 2024-04-12T17:04:52Z |
| format | Article |
| id | doaj.art-f1af8b24e1864bb3899a1bf79c938ff6 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-12T17:04:52Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-f1af8b24e1864bb3899a1bf79c938ff62022-12-22T03:23:59ZengBMCStem Cell Research & Therapy1757-65122022-05-0113111210.1186/s13287-022-02898-wThe stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouseKeonwoo Choi0Sang-Hee Park1Seo-Yeon Park2Sungjoo Kim Yoon3Department of Biomedicine & Health Sciences, The Catholic University of KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of KoreaAbstract Background Hair follicle stem cells (HFSC) play an essential role in the maintenance of hair homeostasis; during the hair cycle, HFSC remain quiescent for most of its duration. The hairpoor mouse (+ /Hr Hp ), an animal model of Marie-Unna hypotrichosis (MUHH), overexpresses hairless in the bulge, inner root sheath, and outer root sheath of HF and shows the same phenotype as in MUHH patients manifesting sparse hair with progression to alopecia with age. The aim of this study was to gain an understanding of the hair cycle and the status of HFSC during the hair cycle of the hairpoor mouse in order to delineate the pathogenesis of MUHH. Methods H&E staining was performed in order to define the state of the hair follicle. FACS analysis and immunostaining were performed at the 1st and 2nd telogen stages for observation of the HFSC. A label retaining assay was performed to determine the quiescent state of hair follicles. qRT-PCR was performed to determine expression of factors involved in niche signaling and Wnt signaling. Results We observed a drastic decrease in the number of hair follicles after the 1st telogen, followed by an intensified disturbance in the hair cycle with shorter anagen as well as 2nd telogen in the hairpoor mouse. A dramatic reduction in the number of CD34 expressing bulges as well as cells was observed at the telogen of the HFs, with prominent high proliferation of bulge cells, suggesting the loss of HFSC quiescence in the hairpoor mouse. The increased cell proliferation in HF was reiterated following the synchronization of the hair cycle, leading to acceleration of HF cycling. Reduced expression of Fgf18 and Bmp6, the factors involved in HFSC quiescence, was observed in the HFSC niche of the hairpoor mouse. In addition, disturbed expression of Wnt signaling molecules including Wnt7b, Wnt10b, and Sfrp1 was observed, which induced the telogen-to-anagen transition of HFs in the hairpoor mouse. Conclusions These results indicate that the quiescent state of HFSC is not properly maintained in the hairpoor mouse, consequently leading HFs to the completely disarrayed hair cycle. These findings may provide an understanding of an underlying mechanism for development of alopecia with age in MUHH patients.https://doi.org/10.1186/s13287-022-02898-wHairpoor mouseMUHHHair follicle stem cellWnt signalingAlopecia |
| spellingShingle | Keonwoo Choi Sang-Hee Park Seo-Yeon Park Sungjoo Kim Yoon The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse Stem Cell Research & Therapy Hairpoor mouse MUHH Hair follicle stem cell Wnt signaling Alopecia |
| title | The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse |
| title_full | The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse |
| title_fullStr | The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse |
| title_full_unstemmed | The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse |
| title_short | The stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse, an MUHH model mouse |
| title_sort | stem cell quiescence and niche signaling is disturbed in the hair follicle of the hairpoor mouse an muhh model mouse |
| topic | Hairpoor mouse MUHH Hair follicle stem cell Wnt signaling Alopecia |
| url | https://doi.org/10.1186/s13287-022-02898-w |
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