Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks.

Stem Cell Reports

Centre de Medicina Regenerativa de Barcelona and Control of Stem Cell Potency Group, Institut de Bioenginyeria de Catalunya, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomaterials y Nanomedicina, 28029 Madrid, Spain; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain. Electronic address:

Published: October 2015

Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625033PMC
http://dx.doi.org/10.1016/j.stemcr.2015.08.016DOI Listing

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