Research Paper Volume 13, Issue 4 pp 4946—4961
Fibroblasts from different body parts exhibit distinct phenotypes in adult progeria Werner syndrome
- 1 Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba 260-8670, Japan
- 2 Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chuo-Ku, Chiba 260-8670, Japan
- 3 Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba 260-8670, Japan
- 4 Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- 5 Department of Diabetes and Metabolism, Asahi General Hospital, Asahi-Shi, Chiba 289-2511, Japan
- 6 Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo 108-8639, Japan
- 7 Department of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba 260-8670, Japan
- 8 Department of Clinical Application, Center for IPS Cell Research and Application (CiRA), Kyoto University, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan
Received: September 5, 2020 Accepted: February 8, 2021 Published: February 24, 2021
https://doi.org/10.18632/aging.202696How to Cite
Copyright: © 2021 Kato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Werner syndrome (WS), also known as adult progeria, is characterized by accelerated aging symptoms from a young age. Patients with WS experience painful intractable skin ulcers with calcifications in their extremities, subcutaneous lipoatrophy, and sarcopenia. However, there is no significant abnormality in the trunk skin, where the subcutaneous fat relatively accumulates. The cause of such differences between the limbs and trunk is unknown. To investigate the underlying mechanism behind these phenomena, we established and analyzed dermal fibroblasts from the foot and trunk of two WS patients. As a result, WS foot-derived fibroblasts showed decreased proliferative potential compared to that from the trunk, which correlated with the telomere shortening. Transcriptome analysis showed increased expression of genes involved in osteogenesis in the foot fibroblasts, while adipogenic and chondrogenic genes were downregulated in comparison with the trunk. Consistent with these findings, the adipogenic and chondrogenic differentiation capacity was significantly decreased in the foot fibroblasts in vitro. On the other hand, the osteogenic potential was mutually maintained and comparable in the foot and trunk fibroblasts. These distinct phenotypes in the foot and trunk fibroblasts are consistent with the clinical symptoms of WS and may partially explain the underlying mechanism of this disease phenotype.
Abbreviations
DEG: differentially expressed gene; FDR: false discovery rate; FPKM: fragments per kilobase million; PD: population doublings; Q-FISH: quantitative fluorescence in situ hybridization; qRT-PCR: quantitative reverse transcription polymerase chain reaction; SEM: standard error of the mean; WS: Werner syndrome.