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Merck

NF1 loss induces senescence during human melanocyte differentiation in an iPSC-based model.

Pigment cell & melanoma research (2015-04-01)
Lionel Larribere, Huizi Wu, Daniel Novak, Marta Galach, Mathias Bernhardt, Elias Orouji, Kasia Weina, Nathalie Knappe, Christos Sachpekidis, Ludmila Umansky, Philipp Beckhove, Viktor Umansky, Sofie De Schepper, Dieter Kaufmann, Robert Ballotti, Corine Bertolotto, Jochen Utikal
ABSTRACT

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(+/-) iPSCs 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.

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Cloruro di magnesio, for molecular biology, 1.00 M±0.01 M
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Formaldeide, for molecular biology, 36.5-38% in H2O
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Cloruro di magnesio, anhydrous, ≥98%
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Triton X-100, laboratory grade
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Glutaraldeide, Grade I, 25% in H2O, specially purified for use as an electron microscopy fixative
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Formaldeide, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
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Glutaraldeide, Grade II, 25% in H2O
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Glutaraldeide, 50 wt. % in H2O
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Cloruro di magnesio, powder, <200 μm
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Cloruro di magnesio, BioUltra, for molecular biology, 2 M in H2O
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Osmium tetroxide solution, suitable for electron microscopy, 4% in H2O
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Cloruro di magnesio, BioReagent, suitable for insect cell culture, ≥97.0%
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Cloruro di magnesio, BioUltra, for molecular biology, ~1 M in H2O
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Glutaraldeide, Grade I, 50% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
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