TY - JOUR
T1 - Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons
AU - Qiang, Liang
AU - Fujita, Ryousuke
AU - Yamashita, Toru
AU - Angulo, Sergio
AU - Rhinn, Herve
AU - Rhee, David
AU - Doege, Claudia
AU - Chau, Lily
AU - Aubry, Laetitia
AU - Vanti, William B.
AU - Moreno, Herman
AU - Abeliovich, Asa
PY - 2011/8/5
Y1 - 2011/8/5
N2 - 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 Aβ, 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.
AB - 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 Aβ, 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.
UR - http://www.scopus.com/inward/record.url?scp=79961131135&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961131135&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2011.07.007
DO - 10.1016/j.cell.2011.07.007
M3 - Article
C2 - 21816272
AN - SCOPUS:79961131135
VL - 146
SP - 359
EP - 371
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -