Gremlin 2 suppresses differentiation of stem/progenitor cells in the human skin
| العنوان: | Gremlin 2 suppresses differentiation of stem/progenitor cells in the human skin |
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| المؤلفون: | Yohei Iwata, Yuichi Hasebe, Masaru Arima, Hirohiko Akamatsu, Mika Kawagishi-Hotta, Inoue Yu, Kazumitsu Sugiura, Seiji Hasegawa |
| المصدر: | Regenerative Therapy, Vol 18, Iss, Pp 191-201 (2021) Regenerative Therapy |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Aging, Medicine (General), Stromal cell, Biomedical Engineering, Human skin, Gremlin2, Biology, Stem cell marker, Biomaterials, R5-920, Dermis, medicine, Homeostasis, IL, Interleukin, Progenitor cell, ITGB1, Integrin beta 1, Tissue homeostasis, Stem cell, KRT14, Keratin 14, QH573-671, integumentary system, Epidermis (botany), KRT10, Keratin 10, TGF-β, Transforming growth factor beta, Cell biology, medicine.anatomical_structure, Differentiation, Original Article, Cytology, PFA, Paraformaldehyde phosphate buffer solution, DAPI, 4′,6-diamidino-2-phenylindole, Developmental Biology |
| الوصف: | Introduction The skin is comprised of various kinds of cells and has three layers, the epidermis, dermis and subcutaneous adipose tissue. Stem cells in each tissue duplicate themselves and differentiate to supply new cells that function in the tissue, and thereby maintain the tissue homeostasis. In contrast, senescent cells accumulate with age and secrete senescence-associated secretory phenotype (SASP) factors that impair surrounding cells and tissues, which lowers the capacity to maintain homeostasis in each tissue. Previously, we found Gremlin 2 (GREM2) as a novel SASP factor in the skin and reported that GREM2 suppressed the differentiation of adipose-derived stromal/stem cells. In the present study, we investigated the effects of GREM2 on stem cells in the epidermis and dermis. Methods To examine whether GREM2 expression and the differentiation levels in the epidermis and dermis are correlated, the expressions of GREM2, stem cell markers, an epidermal differentiation marker Keratin 10 (KRT10) and a dermal differentiation marker type 3 procollagen were examined in the skin samples (n = 14) randomly chosen from the elderly where GREM2 expression level is high and the individual differences of its expression are prominent. Next, to test whether GREM2 affects the differentiation of skin stem cells, cells from two established lines (an epidermal and a dermal stem/progenitor cell model) were cultured and induced to differentiate, and recombinant GREM2 protein was added. Results In the human skin, the expression levels of GREM2 varied among individuals both in the epidermis and dermis. The expression level of GREM2 was not correlated with the number of stem cells, but negatively correlated with those of both an epidermal and a dermal differentiation markers. The expression levels of epidermal differentiation markers were significantly suppressed by the addition of GREM2 in the three-dimensional (3D) epidermis generated with an epidermal stem/progenitor cell model. In addition, by differentiation induction, the expressions of dermal differentiation markers were induced in cells from a dermal stem/progenitor cell model, and the addition of GREM2 significantly suppressed the expressions of the dermal differentiation markers. Conclusions GREM2 expression level did not affect the numbers of stem cells in the epidermis and dermis but affects the differentiation and maturation levels of the tissues, and GREM2 suppressed the differentiation of stem/progenitor cells in vitro. These findings suggest that GREM2 may contribute to the age-related reduction in the capacity to maintain skin homeostasis by suppressing the differentiation of epidermal and dermal stem/progenitor cells. Highlights • In epidermis, the expression levels of GREM2 and KRT10 were negative correlation. • In dermis, the expression levels of GREM2 and Pro-COL3 were negative correlation. • GREM2 suppressed epidermal stem/progenitor cell differentiation in vitro. • GREM2 suppressed dermal stem/progenitor cell differentiation in vitro. |
| تدمد: | 2352-3204 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ec3598740c13b59f1d639a90b26be0f https://doi.org/10.1016/j.reth.2021.06.007 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2ec3598740c13b59f1d639a90b26be0f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523204 |
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