Impact of Progerin Expression on Adipogenesis in Hutchinson-Gilford Progeria Skin-Derived Precursor Cells.

Farah Najdi,Karima Djabali,Peter Krüger

doi:10.3390/cells10071598

Farah Najdi, Karima Djabali + Show 1 more

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https://doi.org/10.3390/cells10071598

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Journal: Cells	Publication Date: Jun 25, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Technical University of Munich

Abstract

Hutchinson–Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs’ adipogenic differentiation potential. Treatment with baricitinib, a JAK–STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation.

Highlights

We showed that the use of baricitinib, a selective JAK 1/2 inhibitor [39], could enhance adipogenesis in skin-derived precursor stem cells (SKPs) derived from Hutchinson–Gilford progeria syndrome (HGPS) fibroblast cultures by delaying senescence
A proportion of HGPS SKPs were shown to differentiate into adipocytes in the presence of ADM
The differentiated cells stained positive for both Oil Red O (ORO) and Bodipy dyes and expressed the adipogenic markers PPARγ and fatty-acid-binding protein 4 (FABP4)

Summary

Introduction

Hutchinson–Gilford progeria syndrome (HGPS, OMIM 176670) is a rare genetic disease that causes premature aging in children. Approximately 135 cases of HGPS are documented worldwide [1]. Affected individuals die at an average age of 14.7 years owing to coronary failure or stroke [2]. Patients with HGPS exhibit several symptoms of normal aging, such as alopecia, atherosclerosis, loss of joint mobility, and severe lipodystrophy [3,4]. The disease results from a de novo mutation in the LMNA, which encodes the A-type nuclear lamin. The C–T transition in exon 11 at nucleotide

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