Skip to main content
. Author manuscript; available in PMC: 2013 Dec 1.
Published in final edited form as: Mol Psychiatry. 2012 Apr 3;17(12):1239–1253. doi: 10.1038/mp.2012.20

Table 3.

Summary of published reports of hiPSC-based models of ASD, SCZD and BD

Disease Reference Genetic mutation Neuronal phenotype hiPSC method Source of cells Patient sex; age at biopsy (years); available phenotypic information
RTT Cheung et al.122 MeCP2(Δ3–4, T158M, R306C) Decreased soma size Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: patient biopsy (1) and Coriell GM11270 (2), GM17880 (3)

  1. Female; 6 growth and developmental delay, inability to walk without assistance, ataxia, nonverbal, has no hand use and constant repetitive hand motions, some tremor, has had epileptic seizures and significant abnormal electroencephalogram, teeth grinding, some sleep difficulties, and breath holding and hyperventilation

  2. Female; 8; normal lysosomal enzymes, clinically affected, classical symptoms

  3. Female; 5; assistance required for walking, delay in growth and development, sleep problems, abnormal EEG with no symptoms of seizures, grinding of teeth, breath holding, hyperventilation, nonverbal, lack of hand usage, repetitive hand motions, difficulty eating and slight refluxes, slight tremor, small feet
RTT Marchettoet al.123 MeCP2(1155del3, Q244X, T158M, R306C) Reduced soma size and spine density, fewer synapses, altered calcium signaling, electrophysiological abnormalities Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: Coriell GM11272 (1), GM16548 (2), GM17880 (3), GM11270 (4)

  1. Female; 3; normal lysosomal enzymes, clinically affected, classical symptoms

  2. Female; 5; clinically affected, slightly curved spine, ambulatory, slight rigidity and spasticity, decreasing head circumference, aberrant sleep patterns, decreased hand usage, repetitive hand motions, breath holding, nonverbal, constipation, decreased hand and feet circulation, rare self-injurious behavior, slight eating problems and refluzes, teeth grinding, slight EEG abnormalities, tremors

  3. Female; 5; assistance required for walking, delay in growth and development, sleep problems, abnormal EEG with no symptoms of seizures, grinding of teeth, breath holding, hyperventilation, nonverbal, lack of hand usage, repetitive hand motions, difficulty eating and slight refluxes, slight tremor, small feet

  4. Female; 8; normal lysosomal enzymes, clinically affected, classical symptoms
RTT Ananiev et al.124 MeCP2(T158M, V247X, R306C) Decrease in nuclear and neuron size Lentivirus: four factors (OCT4, NANOG, SOX2, LIN28), Retrovirus: 4 factors (OCT4, SOX2, KLF4, c-MYC) Fibroblast: Coriell GM17880 (1), GM07982 (2), GM11270 (3)

  1. Female; 5; assistance required for walking, delay in growth and development, sleep problems, abnormal EEG with no symptoms of seizures, grinding of teeth, breath holding, hyperventilation, nonverbal, lack of hand usage, repetitive hand motions, difficulty eating and slight refluxes, slight tremor, small feet

  2. Female; 25; clinically affected, microcephaly, severely retarded, hand wringing starting at age 2, scoliosis at age 12, kyphoscoliosis at age 25, started to lose skills at 2 years old, CT scan at 25 showed atrophy, slow, abnormal EEG, no sleep problems

  3. Female; 8; normal lysosomal enzymes, clinically affected, classical symptoms
Timothy syndrome Paşca et al.129 CACNA1C Defects in calcium signaling, decreased expression of cortical genes, increased production of norepinephrine and dopamine Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: patient biopsy

  1. Female; not stated; not stated

  2. Not stated; not stated; not stated
FXS Urbach et al.127 FMR1 No neurons generated Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: Coriell GM05848 (1), GM07072 (2), GM09497 (3)

  1. Male; 4; increased ear size, elongated face, appears prognathic, mental retardation, undefined connective tissue dysplasia

  2. Male; 22; 9/50 cord blood lymphocytes showed fra(X), mother is an obligate carrier for fra(x)

  3. Male; 28; affected brother, large ears, mental retardation, macro-orchidism, hyperactive, 20% of PBL positive for fra(x)
FXS Sheridanet al.128 FMR1 Fewer and shorter neural processes, increased glial cells with more compact morphology Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: Coriell GM05848 (1), GM05131 (2), GM05185 (3)

  1. Male; 4; increased ear size, elongated face, appears prognathic, mental retardation, undefined connective tissue dysplasia

  2. Male; 3; affected brother and uncle,

  3. Male; 26; 46,fra(X),Y present in 30–50% of PBL
SCZD Chiang et al.131 DISC1 No neurons generated Episome: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: patient biopsy

  1. Male; NA; diagnosed with chronic undifferentiated schizophrenia, auditory and visual hallucinations, multiple delusions and had formal thought disorder

  2. Female; NA; diagnosed chronic paranoid schizophrenia, auditory and visual hallucinations, multiple delusions and had formal thought disorder
SCZD Brennandet al.132 Sporadic Reduced neuronal connectivity, fewer neurites, decreased PSD95 and glutamate receptor expression levels Tetracycline-inducible lentivirus: five factors (OCT4, SOX2, KLF4,c-MYC, LIN28) Fibroblast: Coriell GM02038 (1), GM01792 (2), GM01835 (3), GM02497 (4)

  1. Male; 22; onset at age 6, committed suicide

  2. Male; 26; recurrences of agitation, delusions of persecution, fear of assassination, father and sister affected

  3. Female; 27; schizoaffective disorder, problems of drug abuse, hospitalized, father affected

  4. Male; 23; paralogical thinking, splitting of effect from content, suspiciousness, affective shielding, onset at age 15, hospitalized, positive family history
SCZD Paulsen et al.133 Sporadic Elevated extra-mitochondrial oxygen consumption, increased levels of reactive oxygen species Retrovirus: four factors (OCT4, SOX2, KLF4,c-MYC) Fibroblast: patient biopsy Female; 48; clozapine-resistant

Abbreviations: ASD, autism spectrum disorder; BD, bipolar disorder; EEG, electroencephalogram test; FX, fragile X syndrome; hiPSC, human-derived induced pluripotent stem cell; NA, not applicable; PBL, peripheral blood lymphocyte; RTT, Rett syndrome; SCZD, schizophrenia disorder.