Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes

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RESEARCH PRODUCT

Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes

Manoubia Saidani Xavier Nissan Annachiara De Sandre-giovannoli Annachiara De Sandre-giovannoli Lucile Hoch Jennifer Allouche Alessandra Lo Cicero Sabine Sigaudy Sabine Sigaudy Celine Bruge Christine Baldeschi Anne Laure Egesipe Nicolas Lévy Nicolas Lévy

subject

0301 basic medicine Premature aging congenital hereditary and neonatal diseases and abnormalities Induced Pluripotent Stem Cells lcsh:Medicine Biology Models Biological Article Melanin 03 medical and health sciences Progeria medicine Humans Induced pluripotent stem cell lcsh:Science Pigmentation disorder Melanosome Hypopigmentation Progeria Melanosomes Multidisciplinary integumentary system lcsh:R nutritional and metabolic diseases medicine.disease Progerin Cell biology 030104 developmental biology [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Melanocytes lcsh:Q medicine.symptom Pigmentation Disorders

description

AbstractHutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that leads to premature aging. In this study, we used induced pluripotent stem cells to investigate the hypopigmentation phenotypes observed in patients with progeria. Accordingly, two iPS cell lines were derived from cells from HGPS patients and differentiated into melanocytes. Measurements of melanin content revealed a lower synthesis of melanin in HGPS melanocytes as compared to non-pathologic cells. Analysis of the melanosome maturation process by electron microscopy revealed a lower percentage of mature, fully pigmented melanosomes. Finally, a functional rescue experiment revealed the direct role of progerin in the regulation of melanogenesis. Overall, these results report a new dysregulated pathway in HGPS and open up novel perspectives in the study of pigmentation phenotypes that are associated with normal and pathological aging.

year	journal	country	edition	language
2018-06-01

10.1038/s41598-018-27165-y https://hal-amu.archives-ouvertes.fr/hal-01991357/file/s41598-018-27165-y.pdf

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