Telomere dysfunction impairs epidermal stem cell specification and differentiation by disrupting BMP/pSmad/P63 signaling


Autoři: Na Liu aff001;  Yu Yin aff001;  Haiying Wang aff001;  Zhongcheng Zhou aff001;  Xiaoyan Sheng aff001;  Haifeng Fu aff001;  Renpeng Guo aff001;  Hua Wang aff001;  Jiao Yang aff001;  Peng Gong aff001;  Wen Ning aff001;  Zhenyu Ju aff005;  Yifei Liu aff006;  Lin Liu aff001
Působiště autorů: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China aff001;  Key Laboratory of Bioactive Materials, Ministry of Education, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, China aff002;  School of Medicine, Nankai University, Tianjin, China aff003;  Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China aff004;  Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China aff005;  Yale Fertility Center and Department of OB/GYN, Yale University School of Medicine, New Haven, CT, United States of America aff006
Vyšlo v časopise: Telomere dysfunction impairs epidermal stem cell specification and differentiation by disrupting BMP/pSmad/P63 signaling. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008368
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008368

Souhrn

Telomere shortening is associated with aging and age-associated diseases. Additionally, telomere dysfunction resulting from telomerase gene mutation can lead to premature aging, such as apparent skin atrophy and hair loss. However, the molecular signaling linking telomere dysfunction to skin atrophy remains elusive. Here we show that dysfunctional telomere disrupts BMP/pSmad/P63 signaling, impairing epidermal stem cell specification and differentiation of skin and hair follicles. We find that telomere shortening mediated by Terc loss up-regulates Follistatin (Fst), inhibiting pSmad signaling and down-regulating P63 and epidermal keratins in an ESC differentiation model as well as in adult development of telomere-shortened mice. Mechanistically, short telomeres disrupt PRC2/H3K27me3-mediated repression of Fst. Our findings reveal that skin atrophy due to telomere dysfunction is caused by a previously unappreciated link with Fst and BMP signaling that could be explored in the development of therapies.

Klíčová slova:

Biology and life sciences – Developmental biology – Cell differentiation – Cell biology – Chromosome biology – Chromosomes – Chromosome structure and function – Telomeres – Telomere length – Chromatin – Chromatin modification – DNA methylation – Cellular types – Animal cells – Stem cells – Anatomy – Integumentary system – Skin – Epidermis – Hair follicles – Hair – Genetics – Gene expression – Epigenetics – DNA modification – DNA – Biochemistry – Nucleic acids – Medicine and health sciences


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