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NF1 loss induces senescence during human melanocyte differentiation in an iPSC ‐based model
Author(s) -
Larribere Lionel,
Wu Huizi,
Novak Daniel,
Galach Marta,
Bernhardt Mathias,
Orouji Elias,
Weina Kasia,
Knappe Nathalie,
Sachpekidis Christos,
Umansky Ludmila,
Beckhove Philipp,
Umansky Viktor,
De Schepper Sofie,
Kaufmann Dieter,
Ballotti Robert,
Bertolotto Corine,
Utikal Jochen
Publication year - 2015
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12369
Subject(s) - induced pluripotent stem cell , melanocyte , neurofibromatosis , biology , microbiology and biotechnology , senescence , lineage (genetic) , neuroscience , cancer research , genetics , embryonic stem cell , melanoma , gene
Summary Neurofibromatosis type 1 (NF1) is a frequent genetic disease leading to the development of Schwann cell‐derived neurofibromas or melanocytic lesions called café‐au‐lait macules (CALMs). The molecular mechanisms involved in CALMs formation remain largely unknown. In this report, we show for the first time pathophysiological mechanisms of abnormal melanocyte differentiation in a human NF1 +/− ‐induced pluripotent stem cell ( iPSC )‐based model. We demonstrate that NF1 patient‐derived fibroblasts can be successfully reprogrammed in NF1 +/− iPSC s with active RAS signaling and that NF1 loss induces senescence during melanocyte differentiation as well as in patient's‐derived CALMs, revealing a new role for NF1 in the melanocyte lineage.