Journal article
Directed Conversion of Alzheimer's Disease Patient Skin Fibroblasts into Functional Neurons
Cell, v 146(3), pp 359-371
05 Aug 2011
PMID: 21816272
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Directed conversion of mature human cells, as from fibroblasts to neurons, is of potential clinical utility for neurological disease modeling as well as cell therapeutics. Here, we describe the efficient generation of human-induced neuronal (hiN) cells from adult skin fibroblasts of unaffected individuals and Alzheimer's patients, using virally transduced transcription regulators and extrinsic support factors. hiN cells from unaffected individuals display morphological, electrophysiological, and gene expression profiles that typify glutamatergic forebrain neurons and are competent to integrate functionally into the rodent CNS. hiN cells from familial Alzheimer disease (FAD) patients with presenilin-1 or -2 mutations exhibit altered processing and localization of amyloid precursor protein (APP) and increased production of Ab, relative to the source patient fibroblasts or hiN cells from unaffected individuals. Together, our findings demonstrate directed conversion of human fibroblasts to a neuronal phenotype and reveal cell type-selective pathology in hiN cells derived from FAD patients.
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Details
- Title
- Directed Conversion of Alzheimer's Disease Patient Skin Fibroblasts into Functional Neurons
- Creators
- Liang Qiang - Columbia UniversityRyousuke Fujita - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USAToru Yamashita - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USASergio Angulo - SUNY Downstate Medical CenterHerve Rhinn - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USADavid Rhee - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USAClaudia Doege - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USALily Chau - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USALaetitia Aubry - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USAWilliam B. Vanti - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USAHerman Moreno - SUNY Downstate Medical CenterAsa Abeliovich - Departments of Pathology, Cell Biology, and Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USA
- Publication Details
- Cell, v 146(3), pp 359-371
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- Helmsley Foundation AG027476 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K08AG027476 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) C024402; C024403 / New York State Stem Cell Science NYSTEM R01NS064433 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000293570500011
- Scopus ID
- 2-s2.0-79961131135
- Other Identifier
- 991019201377204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology