Supplementary Table 1 | Diseases modelled with iPS cells
Disease
Molecular defect of donor
cell
Cell type
differentiated
from iPS cells
Disease
phenocopied in
Drug or functional
differentiated
tests
cells
Neurological
Amyotrophic
Heterozygous
Motor neurons
lateral sclerosis
Leu144Phe mutation in
and glial cells
(ALS)1
SOD1
Spinal muscular
Mutations in SMN1
atrophy (SMA)2
Neurons and
ND
No
Yes
VPA and
astrocytes, and
tobramycin
mature motor
ameliorate
neurons
phenotype
Parkinson’s
Multifactorial; mutations
Dopaminergic
disease3–6
in LRRK2 and/or SNCA
neurons
No
Transplanted
Parkinson’s
disease iPS-cellderived neurons
ameliorate
phenotype in rats
with Parkinson’s
disease
Huntington’s
72 CAG repeats in the
disease3
huntingtin gene
Down’s
Trisomy 21
syndrome3
None
NA
No
Teratoma with
Yes
No
None
NA
No
Central nervous-
Yes
Kinetin
tissue from each
of the three germ
layers
Fragile X
CGG triplet repeat
syndrome7
expansion resulting in the
silencing of FMR1
Familial
dysautonomia8
Mutation in IKBKAP
system lineage,
ameliorates
peripheral
phenotype
neurons,
haematopoietic
cells, endothelial
cells and
endodermal cells
Rett’s
Heterozygous mutation in
Neural
syndrome9,10
MECP2
progenitor cells
Yes
IGF1 and high
dose gentamicin
treatment
ameliorates
phenotype
Mucopolysacchar
Homozygous mutation in
Neural stem
idosis type IIIB
NAGLU
cells and
NAGLU enzyme
differentiated
replacement is
neurons
sufficient to
(MPS
IIIB)11
Partially
Exogenous
prevent pathology
Schizophrenia12
Complex trait
Neurons
Yes
Treatment with
loxapine
improves
neuronal
connectivity; no
improvement with
clozapine,
olanzapine,
risperidone or
thioridazine
X-linked
Mutation in ABCD1
adrenoleukodystr
ophy
Oligodendrocyte
Partially
s and neurons
Treatment with
lovastatin or 4-
(X-ALD)13,
phenylbutyrate
childhood
ameliorates
cerebral ALD
phenotype
(CCALD) and
adrenomyeloneur
opathy (AMN)
Haematological
ADA SCID3
Mutation or deletion in
None
ND
No
Haematopoietic
No (corrected)
No
ADA
Fanconi’s
FAA and FAD2 corrected
anaemia14
Schwachman–
cells
Multifactorial
None
NA
No
Sickle-cell
Homozygous HbS
None
NA
No
anaemia15,16
mutation
-Thalassaemia17
Homozygous deletion in
Haematopoietic
ND
No
the -globin gene
cells
Bodian–Diamond
syndrome3
Polycythaemia
Heterozygous Val617Phe
Haematopoietic
Partially
No
vera18
mutation in JAK2
progenitors
None
NA
No
None
NA
No
-Cell-like cells
ND
No
(CD34+CD35+)
Primary
Heterozygous mutation in
myelofibrosis18
JAK2
Metabolic
Lesch–Nyhan
Heterozygous mutation in
syndrome
HPRT1
(carrier)3,4,19
Type 1
Multifactorial; unknown
diabetes3,20
(express
somatostatin,
glucagon and
insulin; glucoseresponsive)
Mutation in GBA
None
NA
No
1-Antitrypsin
Homozygous mutation in
Hepatocyte-like
Yes
No
deficiency
the 1-antitrypsin gene
cells (fetal)
Glycogen
Defect in glucose-6-
Hepatocyte-like
Yes
No
storage disease
phosphate gene
cells (fetal)
Familial
Autosomal dominant
Hepatocyte-like
Yes
No
hypercholesterol
mutation in LDLR
cells (fetal)
Deletion in UGT1A1
Hepatocyte-like
ND
No
ND
No
Yes
No
ND
No
No
No
Gaucher’s
disease, type
III3
(A1ATD)15,21
Ia (GSD1a)21,22
aemia21
Crigler–Najjar
syndrome21,22
Hereditary
cells (fetal)
Mutation in FAHD1
tyrosinaemia,
Hepatocyte-like
cells (fetal)
type 121,22
Pompe disease23
Knockout of Gaa
Skeletal muscle
cells
Progressive
Multifactorial
familial
Hepatocyte-like
cells (fetal)
cholestasis22
Hurler syndrome
(MPS IH)24
Genetic defect in IDUA
Haematopoietic
cells
Cardiovascular
LEOPARD
Heterozygous mutation in
syndrome25
PTPN11
Type 1 long QT
Dominant mutation in
syndrome26
KCNQ1
Type 2 long QT
Missense mutation in
syndrome27
KCNH2
Cardiomyocytes
Yes
No
Cardiomyocytes
Yes
No
Cardiomyocytes
Yes
E-4031 and
cisapride
aggravate
disease
phenotype;
nifedipine,
pinacidil and
ranolazine
ameliorate some
aspects of
disease
phenotype
Primary
immunodeficienc
y
SCID28 or leaky
Mutation in RAG1
None
NA
No
Mutation in RAG1
None
NA
No
Mutation in RMRP
None
NA
No
Herpes simplex
Mutation in STAT1 or
Mature cell types
No
No
encephalitis
TLR3
of the central
None
NA
No
None
NA
No
None
NA
No
SCID
Omenn
syndrome
(OS)28
Cartilage-hair
hypoplasia
(CHH)28
(HSE)28
nervous system
Other category
Duchenne
Deletion in the dystrophin
muscular
gene
dystrophy3,29
Becker muscular
Unidentified mutation in
dystrophy3
dystrophin
Dyskeratosis
Deletion in DKC1
congenita
(DC)30
Cystic fibrosis15,31
Homozygous deletion in
None
NA
No
Trinucleotide GAA repeat
Sensory and
Partially
No
expansion in FXN
peripheral
Yes
-Tocopherol
CFTR
Friedreich’s
ataxia
(FRDA)32
neurons, and
cardiomyocytes
Retinitis
Heterogeneity in
Retinal
pigmentosa33
causative genes and
progenitors,
ameliorates
mutations: mutations in
photoreceptor
disease
RP9, RP1, PRPH2 or
precursors,
phenotype in a
RHO
retinal-pigment
mutated RP9
epithelial cells
background but
and rod
not in mutated
photoreceptor
RP1, PRPH2 or
cells
RHO
backgrounds;
ascorbic acid and
-carotene
treatment has no
effect on
phenotype
Recessive
Mutation in COL7A1
Haematopoietic
Partially
Gene correction
dystrophic
cells, and
with Col7a1
epidermolysis
epidermis-like
expression
bullosa (RDEB)34
keratinocytes
plasmid
that differentiate
increases
into cells of all
COL7A1 protein
three germ
expression
layers in vivo
compared with
wild-type cells
Scleroderma15
Unknown
None
NA
No
Osteogenesis
Mutation in COL1A2
None
NA
No
imperfecta19
ABCD1, ATP-binding cassette, sub-family D, member 1; ADA, adenine deaminase; CFTR, cystic fibrosis
transmembrane conductance regulator; COL1A2, 2-chain of type I collagen; COL7A1, 1-chain of type
VII collagen; DKC1, dyskerin; FAA, Fanconi’s anaemia, complementation group A; FAD2, Fanconi’s
anaemia, complementation group D2; FAHD1, fumarylacetoacetate hydrolase; FMR1, fragile X mental
retardation 1; FXN, frataxin; Gaa, acid α-glucosidase; GBA, acid -glucosidase; HbS, sickle
haemoglobin; HPRT1, hypoxanthine phosphoribosyltransferase 1; IDUA, -L-iduronidase; IGF1, insulin-
like growth factor 1; JAK2, Janus kinase 2; KCNH2, potassium voltage-gated channel, subfamily H (eagrelated), member 2; KCNQ1, potassium voltage-gated channel, KQT-like subfamily, member 1; LDLR,
low-density lipoprotein receptor; LRRK2, leucine-rich repeat kinase 2; MECP2, methyl CpG binding
protein 2; NA, not applicable; NAGLU, -N-acetylglucosaminidase; ND not determined; PRPH2,
peripherin 2; PTPN11, protein tyrosine phosphatase, non-receptor type 11; RAG1, recombination
activating gene 1; RHO, rhodopsin; RMRP, RNA component of mitochondrial-RNA-processing
endoribonuclease; RP, retinitis pigmentosa; SCID, severe combined immunodeficiency; SMN1, survival
of motor neuron 1; SNCA, -synuclein; SOD1, superoxide dismutase 1; STAT1, signal transducer and
activator of transcription 1; TLR3, Toll-like receptor 3; UGT1A1, UDP glucuronosyltransferase 1 family,
polypeptide A1; VPA, valproic acid.
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