Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. DMD is caused by defective expression of the DMD gene, which encodes for dystrophin, a component of the dystrophin glycoprotein complex. In muscle fibers, this protein complex plays a critical role in maintaining muscle membrane integrity. Emerging studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as healthy muscle stem cells, and their impairment contributes to disease progression. Deficiencies in muscle stem cell function include impaired establishment of cell polarity leading to defective asymmetric stem cell division, reduced myogenic commitment, impaired differentiation, altered metabolism, and enhanced entry into senescence. Altogether, these findings indicate that DMD muscle stem cells are dysfunctional and have impaired regenerative potential. Although recent advances in adeno-associated vector and antisense oligonucleotide-mediated mechanisms for gene therapy have shown clinical promise, the current therapeutic strategies for muscular dystrophy do not effectively target muscle stem cells and do not address the deficiencies in muscle stem cell function. Here, we discuss the merits of restoring endogenous muscle stem cell function in degenerating muscle as a viable regenerative medicine strategy to mitigate DMD.

1.
Acharyya
S
,
Butchbach
ME
,
Sahenk
Z
,
Wang
H
,
Saji
M
,
Carathers
M
,
.
Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia
.
Cancer Cell
.
2005
;
8
(
5
):
421
32
.
2.
Alderton
JM
,
Steinhardt
RA
.
Calcium influx through calcium leak channels is responsible for the elevated levels of calcium-dependent proteolysis in dystrophic myotubes
.
J Biol Chem
.
2000
;
275
(
13
):
9452
60
.
3.
Alexander
MS
,
Rozkalne
A
,
Colletta
A
,
Spinazzola
JM
,
Johnson
S
,
Rahimov
F
,
.
CD82 Is a Marker for Prospective Isolation of Human Muscle Satellite Cells and Is Linked to Muscular Dystrophies
.
Cell Stem Cell
.
2016
;
19
(
6
):
800
7
.
4.
Allen
DG
,
Whitehead
NP
,
Froehner
SC
.
Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy
.
Physiol Rev
.
2016
;
96
(
1
):
253
305
.
5.
Arnett
AL
,
Konieczny
P
,
Ramos
JN
,
Hall
J
,
Odom
G
,
Yablonka-Reuveni
Z
,
.
Adeno-associated viral (AAV) vectors do not efficiently target muscle satellite cells
.
Mol Ther Methods Clin Dev
.
2014
;
1
:
14038
.
6.
Bankole
LC
,
Feasson
L
,
Ponsot
E
,
Kadi
F
.
Fibre type-specific satellite cell content in two models of muscle disease
.
Histopathology
.
2013
;
63
(
6
):
826
32
.
7.
Barton
ER
,
Morris
L
,
Kawana
M
,
Bish
LT
,
Toursel
T
.
Systemic administration of L-arginine benefits mdx skeletal muscle function
.
Muscle Nerve
.
2005
;
32
(
6
):
751
60
.
8.
Benayoun
BA
,
Pollina
EA
,
Ucar
D
,
Mahmoudi
S
,
Karra
K
,
Wong
ED
,
.
H3K4me3 breadth is linked to cell identity and transcriptional consistency
.
Cell
.
2014
;
158
(
3
):
673
88
.
9.
Biressi
S
,
Rando
TA
.
Heterogeneity in the muscle satellite cell population
.
Semin Cell Dev Biol
.
2010
;
21
(
8
):
845
54
.
10.
Birnkrant
DJ
,
Bushby
K
,
Bann
CM
,
Apkon
SD
,
Blackwell
A
,
Brumbaugh
D
,
.
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management
.
Lancet Neurol
.
2018
;
17
(
3
):
251
67
.
11.
Bladen
CL
,
Salgado
D
,
Monges
S
,
Foncuberta
ME
,
Kekou
K
,
Kosma
K
,
.
The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations
.
Hum Mutat
.
2015
;
36
(
4
):
395
402
.
12.
Blankinship
MJ
,
Gregorevic
P
,
Allen
JM
,
Harper
SQ
,
Harper
H
,
Halbert
CL
,
.
Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6
.
Mol Ther
.
2004
;
10
(
4
):
671
8
.
13.
Bodensteiner
JB
,
Engel
AG
.
Intracellular calcium accumulation in Duchenne dystrophy and other myopathies: a study of 567,000 muscle fibers in 114 biopsies
.
Neurology
.
1978
;
28
(
5
):
439
.
14.
Boscolo Sesillo
F
,
Fox
D
,
Sacco
A
.
Muscle Stem Cells Give Rise to Rhabdomyosarcomas in a Severe Mouse Model of Duchenne Muscular Dystrophy
.
Cell Rep
.
2019
;
26
(
3
):
689
e6
.
15.
Bowles
DE
,
McPhee
SW
,
Li
C
,
Gray
SJ
,
Samulski
JJ
,
Camp
AS
,
.
Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector
.
Mol Ther
.
2012
;
20
(
2
):
443
55
.
16.
Boyer
JG
,
Han
S
,
Prasad
V
,
Khalil
H
,
Vagnozzi
RJ
,
Molkentin
JD
.
Satellite cell depletion in early adulthood attenuates muscular dystrophy pathogenesis
.
bioRxiv
.
2019
:
857433
.
17.
Bulfield
G
,
Siller
WG
,
Wight
PA
,
Moore
KJ
.
X chromosome-linked muscular dystrophy (mdx) in the mouse
.
Proc Natl Acad Sci USA
.
1984
;
81
(
4
):
1189
92
.
18.
Bushby
K
,
Finkel
R
,
Birnkrant
DJ
,
Case
LE
,
Clemens
PR
,
Cripe
L
,
.
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management
.
Lancet Neurol
.
2010
;
9
(
1
):
77
93
.
19.
Campbell
KP
,
Kahl
SD
.
Association of dystrophin and an integral membrane glycoprotein
.
Nature
.
1989
;
338
(
6212
):
259
62
.
20.
Campisi
J
.
Aging, Cellular Senescence, and Cancer
.
Annu Rev Physiol
.
2013
;
75
(
1
):
685
705
.
21.
Casuso
RA
,
Huertas
JR
.
The emerging role of skeletal muscle mitochondrial dynamics in exercise and ageing
.
Ageing Res Rev
.
2020
;
58
:
101025
.
22.
Chakkalakal
JV
,
Stocksley
MA
,
Harrison
MA
,
Angus
LM
,
Deschênes-Furry
J
,
St-Pierre
S
,
.
Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling
.
Proc Natl Acad Sci USA
.
2003
;
100
(
13
):
7791
6
.
23.
Chal
J
,
Oginuma
M
,
Al Tanoury
Z
,
Gobert
B
,
Sumara
O
,
Hick
A
,
.
Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy
.
Nat Biotechnol
.
2015
;
33
(
9
):
962
9
.
24.
Chamberlain
JS
,
Metzger
J
,
Reyes
M
,
Townsend
D
,
Faulkner
JA
.
Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma
.
FASEB J
.
2007
;
21
(
9
):
2195
204
.
25.
Chan
S
,
Head
SI
.
The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy
.
Exp Physiol
.
2011
;
96
(
6
):
564
71
.
26.
Chang
NC
,
Chevalier
FP
,
Rudnicki
MA
.
Satellite Cells in Muscular Dystrophy - Lost in Polarity
.
Trends Mol Med
.
2016
;
22
(
6
):
479
96
.
27.
Chang
NC
,
Sincennes
MC
,
Chevalier
FP
,
Brun
CE
,
Lacaria
M
,
Segalés
J
,
.
The Dystrophin Glycoprotein Complex Regulates the Epigenetic Activation of Muscle Stem Cell Commitment
.
Cell Stem Cell
.
2018
;
22
(
5
):
755
e6
.
28.
Chapman
J
,
Fielder
E
,
Passos
JF
.
Mitochondrial dysfunction and cell senescence: deciphering a complex relationship
.
FEBS Lett
.
2019
;
593
(
13
):
1566
79
.
29.
Cooper
RN
,
Tajbakhsh
S
,
Mouly
V
,
Cossu
G
,
Buckingham
M
,
Butler-Browne
GS
.
In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle
.
J Cell Sci
.
1999
;
112(Pt 17)
:
2895
901
.
30.
Cornelison
DD
,
Wold
BJ
.
Single-Cell Analysis of Regulatory Gene Expression in Quiescent and Activated Mouse Skeletal Muscle Satellite Cells
.
Dev Biol
.
1997
;
191
(
2
):
270
83
.
31.
Cramer
Z
,
Sadek
J
,
Vazquez
GG
,
Di Marco
S
,
Pause
A
,
Pelletier
J
,
.
eIF4A inhibition prevents the onset of cytokine-induced muscle wasting by blocking the STAT3 and iNOS pathways
.
Sci Rep
.
2018
;
8
(
1
):
8414
.
32.
De Arcangelis
V
,
Serra
F
,
Cogoni
C
,
Vivarelli
E
,
Monaco
L
,
Naro
F
.
β1-syntrophin modulation by miR-222 in mdx mice
.
PLoS One
.
2010
;
5
(
8
).http://dx.doi.org/10.1371/journal.pone.0012098
33.
De Micheli
AJ
,
Laurilliard
EJ
,
Heinke
CL
,
Ravichandran
H
,
Fraczek
P
,
Soueid-Baumgarten
S
,
.
Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration
.
Cell Rep
.
2020
;
30
(
10
):
3583
3595e5
.
34.
Deconinck
AE
,
Rafael
JA
,
Skinner
JA
,
Brown
SC
,
Potter
AC
,
Metzinger
L
,
.
Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
.
Cell
.
1997
;
90
(
4
):
717
27
.
35.
Deconinck
N
,
Tinsley
J
,
De Backer
F
,
Fisher
R
,
Kahn
D
,
Phelps
S
,
.
Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice
.
Nat Med
.
1997
;
3
(
11
):
1216
21
.
36.
Dell
OS
,
Juan
AH
,
Ko
K-D
,
Naz
F
,
Perovanovic
J
,
.
Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions
.
Development
.
2019
;
146
(
12
):
dev174177
.
37.
Di Marco
S
,
Mazroui
R
,
Dallaire
P
,
Chittur
S
,
Tenenbaum
SA
,
Radzioch
D
,
.
NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release
.
Mol Cell Biol
.
2005
;
25
(
15
):
6533
45
.
38.
Doherty
TJ
.
Invited review: aging and sarcopenia
.
J Appl Physiol
.
2003
;
95
(
4
):
1717
27
.
39.
Duan
D
.
Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy
.
Mol Ther
.
2018
;
26
(
10
):
2337
56
.
40.
Dumont
NA
,
Wang
YX
,
von Maltzahn
J
,
Pasut
A
,
Bentzinger
CF
,
Brun
CE
,
.
Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division
.
Nat Med
.
2015
;
21
(
12
):
1455
63
.
41.
Emery
AE
,
Muntoni
F
,
Quinlivan
RC
.
Duchenne muscular dystrophy
.
Oxford
:
Oxford University Press
;
2015
.
42.
Ervasti
JM
,
Ohlendieck
K
,
Kahl
SD
,
Gaver
MG
,
Campbell
KP
.
Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle
.
Nature
.
1990
;
345
(
6273
):
315
9
.
43.
Faber
RM
,
Hall
JK
,
Chamberlain
JS
,
Banks
GB
.
Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice
.
Skelet Muscle
.
2014
;
4
:
10
.
44.
Falzarano
MS
,
Scotton
C
,
Passarelli
C
,
Ferlini
A
.
Duchenne Muscular Dystrophy: From Diagnosis to Therapy
.
Molecules
.
2015
;
20
(
10
):
18168
84
.
45.
Fearon
K
,
Strasser
F
,
Anker
SD
,
Bosaeus
I
,
Bruera
E
,
Fainsinger
RL
,
.
Definition and classification of cancer cachexia: an international consensus
.
Lancet Oncol
.
2011
;
12
(
5
):
489
95
.
46.
Fiacco
E
,
Castagnetti
F
,
Bianconi
V
,
Madaro
L
,
De Bardi
M
,
Nazio
F
,
.
Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles
.
Cell Death Differ
.
2016
;
23
(
11
):
1839
49
.
47.
Fong
PY
,
Turner
PR
,
Denetclaw
WF
,
Steinhardt
RA
.
Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin
.
Science
.
1990
;
250
(
4981
):
673
6
.
48.
Gao
X
,
Han
G
,
Yin
H
.
Recent Advances in AON-Mediated Exon-Skipping Therapy for Duchenne Muscular Dystrophy
.
Springer
;
2019
. p.
339
54
.
Muscle Gene Therapy
.
49.
García-Prat
L
,
Martínez-Vicente
M
,
Perdiguero
E
,
Ortet
L
,
Rodríguez-Ubreva
J
,
Rebollo
E
,
.
Autophagy maintains stemness by preventing senescence
.
Nature
.
2016
;
529
(
7584
):
37
42
.
50.
Garcia-Prat
L
,
Perdiguero
E
,
Alonso-Martin
S
,
Dell’Orso
S
,
Ravichandran
S
,
Brooks
SR
,
.
FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
.
Nat Cell Biol
.
2020
;
22
(
11
):
1307
18
.
51.
Gregorevic
P
,
Blankinship
MJ
,
Allen
JM
,
Crawford
RW
,
Meuse
L
,
Miller
DG
,
.
Systemic delivery of genes to striated muscles using adeno-associated viral vectors
.
Nat Med
.
2004
;
10
(
8
):
828
34
.
52.
Gurevich
DB
,
Nguyen
PD
,
Siegel
AL
,
Ehrlich
OV
,
Sonntag
C
,
Phan
JM
,
.
Asymmetric division of clonal muscle stem cells coordinates muscle regeneration in vivo
.
Science
.
2016
;
353
(
6295
):
aad9969
.
53.
Guttridge
DC
,
Mayo
MW
,
Madrid
LV
,
Wang
CY
,
Baldwin
AS
Jr
.
NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia
.
Science
.
2000
;
289
(
5488
):
2363
6
.
54.
Hayes
MN
,
McCarthy
K
,
Jin
A
,
Oliveira
ML
,
Iyer
S
,
Garcia
SP
,
.
Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma
.
Cell Stem Cell
.
2018
;
22
(
3
):
414
e6
.
55.
He
WA
,
Berardi
E
,
Cardillo
VM
,
Acharyya
S
,
Aulino
P
,
Thomas-Ahner
J
,
.
NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia
.
J Clin Invest
.
2013
;
123
(
11
):
4821
35
.
56.
Hernández-Hernández
JM
,
García-González
EG
,
Brun
CE
,
Rudnicki
MA
.
The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration
.
Semin Cell Dev Biol
.
2017
;
72
:
10
18
.
57.
Heslop
L
,
Morgan
JE
,
Partridge
TA
.
Evidence for a myogenic stem cell that is exhausted in dystrophic muscle
.
J Cell Sci
.
2000
;
113 (Pt 12)
:
2299
.
58.
Hoffman
EP
,
Brown
RH
Jr.
,
Kunkel
LM
.
Dystrophin: the protein product of the Duchenne muscular dystrophy locus
.
Cell
.
1987
;
51
(
6
):
919
28
.
59.
Hood
DA
,
Memme
JM
,
Oliveira
AN
,
Triolo
M
.
Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging
.
Annu Rev Physiol
.
2019
;
81
(
1
):
19
41
.
60.
Hughes
DC
,
Marcotte
GR
,
Marshall
AG
,
West
DWD
,
Baehr
LM
,
Wallace
MA
,
.
Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability
.
J Gerontol A Biol Sci Med Sci
.
2017
;
72
(
5
):
640
8
.
61.
Hughes
MC
,
Ramos
SV
,
Turnbull
PC
,
Rebalka
IA
,
Cao
A
,
Monaco
CMF
,
.
Early myopathy in Duchenne muscular dystrophy is associated with elevated mitochondrial H
.
J Cachexia Sarcopenia Muscle
.
2019
;
10
(
3
):
643
61
.
62.
Inaba
S
,
Hinohara
A
,
Tachibana
M
,
Tsujikawa
K
,
Fukada
SI
.
Muscle regeneration is disrupted by cancer cachexia without loss of muscle stem cell potential
.
PLoS One
.
2018
;
13
(
10
):
e0205467
.
63.
Joseph
J
,
Cho
DS
,
Doles
JD
.
Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy
.
Metabolites
.
2018
;
8
(
4
).http://dx.doi.org/10.3390/metabo8040061
64.
Kawabe
Y
,
Wang
YX
,
McKinnell
IW
,
Bedford
MT
,
Rudnicki
MA
.
Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during asymmetric satellite stem cell divisions
.
Cell Stem Cell
.
2012
;
11
(
3
):
333
45
.
65.
Khan
MA
.
Corticosteroid therapy in Duchenne muscular dystrophy
.
J Neurol Sci
.
1993
;
120
(
1
):
8
14
.
66.
Kharraz
Y
,
Guerra
J
,
Pessina
P
,
Serrano
AL
,
Munoz-Canoves
P
.
Understanding the process of fibrosis in Duchenne muscular dystrophy
.
Biomed Res Int
.
2014
;
2014
:
965631
.
67.
Khurana
TS
,
Rosmarin
AG
,
Shang
J
,
Krag
TO
,
Das
S
,
Gammeltoft
S
.
Activation of utrophin promoter by heregulin via the ets-related transcription factor complex GA-binding protein alpha/beta
.
Mol Biol Cell
.
1999
;
10
(
6
):
2075
86
.
68.
Kimmel
JC
,
Hwang
AB
,
Scaramozza
A
,
Marshall
WF
,
Brack
AS
.
Aging induces aberrant state transition kinetics in murine muscle stem cells
.
Development
.
2020
;
147
(
9
):
dev183855
.
69.
Kindstedt
E
,
Holm
CK
,
Sulniute
R
,
Martinez-Carrasco
I
,
Lundmark
R
,
Lundberg
P
.
CCL11, a novel mediator of inflammatory bone resorption
.
Sci Rep
.
2017
;
7
(
1
):
5334
.
70.
Koenig
M
,
Hoffman
E
,
Bertelson
C
,
Monaco
A
,
Feener
C
,
Kunkel
L
.
Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals
.
Cell
.
1987
;
50
(
3
):
509
17
.
71.
Koenig
M
,
Monaco
A
,
Kunkel
L
.
The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein
.
Cell
.
1988
;
53
(
2
):
219
28
.
72.
Koo
T
,
Wood
MJ
.
Clinical trials using antisense oligonucleotides in duchenne muscular dystrophy
.
Hum Gene Ther
.
2013
;
24
(
5
):
479
88
.
73.
Kottlors
M
,
Kirschner
J
.
Elevated satellite cell number in Duchenne muscular dystrophy
.
Cell Tissue Res
.
2010
;
340
(
3
):
541
8
.
74.
Kuang
S
,
Kuroda
K
,
Le Grand
F
,
Rudnicki
MA
.
Asymmetric self-renewal and commitment of satellite stem cells in muscle
.
Cell
.
2007
;
129
(
5
):
999
1010
.
75.
Latella
L
,
Dall’Agnese
A
,
Boscolo
FS
,
Nardoni
C
,
Cosentino
M
,
Lahm
A
,
.
DNA damage signaling mediates the functional antagonism between replicative senescence and terminal muscle differentiation
.
Genes Dev
.
2017
;
31
(
7
):
648
59
.
76.
Le Grand
F
,
Jones
AE
,
Seale
V
,
Scime
A
,
Rudnicki
MA
.
Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells
.
Cell Stem Cell
.
2009
;
4
(
6
):
535
47
.
77.
Lin
C
,
Han
G
,
Ning
H
,
Song
J
,
Ran
N
,
Yi
X
,
.
Glycine Enhances Satellite Cell Proliferation, Cell Transplantation, and Oligonucleotide Efficacy in Dystrophic Muscle
.
Mol Ther
.
2020
;
28
(
5
):
1339
58
.
78.
Lu
A
,
Guo
P
,
Wang
L
,
Tseng
C
,
Huard
M
,
Allen
C
,
.
Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy
.
Sci Rep
.
2020
;
10
(
1
):
7075
.
79.
Ma
JF
,
Sanchez
BJ
,
Hall
DT
,
Tremblay
AK
,
Di Marco
S
,
Gallouzi
IE
.
STAT3 promotes IFNgamma/TNFalpha-induced muscle wasting in an NF-kappaB-dependent and IL-6-independent manner
.
EMBO Mol Med
.
2017
;
9
(
5
):
622
37
.
80.
Madaro
L
,
Torcinaro
A
,
De Bardi
M
,
Contino
FF
,
Pelizzola
M
,
Diaferia
GR
,
.
Macrophages fine tune satellite cell fate in dystrophic skeletal muscle of mdx mice
.
PLoS Genet
.
2019
;
15
(
10
):
e1008408
.
81.
Mahoney
WM
, Jr.
,
Gunaje
J
,
Daum
G
,
Dong
XR
,
Majesky
MW
.
Regulator of G-protein signaling -- 5 (RGS5) is a novel repressor of hedgehog signaling
.
PLoS One
.
2013
;
8
(
4
):
e61421
.
82.
Maier
F
,
Bornemann
A
.
Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies
.
Muscle Nerve
.
1999
;
22
(
5
):
578
83
.
83.
Manzur
AY
,
Kuntzer
T
,
Pike
M
,
Swan
AV
.
Glucocorticoid corticosteroids for Duchenne muscular dystrophy
.
Cochrane Database Syst Rev
.
2008
;
1
:
CD003725
.
84.
Mauro
A
.
Satellite cell of skeletal muscle fibers
.
J Biophys Biochem Cytol
.
1961
;
9
(
2
):
493
5
.
85.
McCaffrey
LM
,
Macara
IG
.
Signaling pathways in cell polarity
.
Cold Spring Harb Perspect Biol
.
2012
;
4
(
6
):
a009654
.
86.
McCoin
CS
,
Knotts
TA
,
Ono-Moore
KD
,
Oort
PJ
,
Adams
SH
.
Long-chain acylcarnitines activate cell stress and myokine release in C2C12 myotubes: calcium-dependent and -independent effects
.
Am J Physiol Endocrinol Metab
.
2015
;
308
(
11
):
E990
E1000
.
87.
McKinnell
IW
,
Ishibashi
J
,
Le Grand
F
,
Punch
VG
,
Addicks
GC
,
Greenblatt
JF
,
.
Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex
.
Nat Cell Biol
.
2008
;
10
(
1
):
77
84
.
88.
Miura
P
,
Jasmin
BJ
.
Utrophin upregulation for treating Duchenne or Becker muscular dystrophy: how close are we
?
Trends Mol Med
.
2006
;
12
(
3
):
122
9
.
89.
Mohiuddin
M
,
Choi
JJ
,
Lee
NH
,
Jeong
H
,
Anderson
SE
,
Han
WM
,
.
Transplantation of Muscle Stem Cell Mitochondria Rejuvenates the Bioenergetic Function of Dystrophic Muscle
.
bioRxiv
.
2020
. 2020.04.17.017822.
90.
Muntoni
F
,
Fisher
I
,
Morgan
JE
,
Abraham
D
.
Steroids in Duchenne muscular dystrophy: from clinical trials to genomic research
.
Neuromuscul Disord
.
2002
;
12
(
Suppl 1
):
S162
5
.
91.
Nance
ME
,
Shi
R
,
Hakim
CH
,
Wasala
NB
,
Yue
Y
,
Pan
X
,
.
AAV9 Edits Muscle Stem Cells in Normal and Dystrophic Adult Mice
.
Mol Ther
.
2019
;
27
(
9
):
1568
85
.
92.
Naya
FJ
,
Olson
E
.
MEF2: a transcriptional target for signaling pathways controlling skeletal muscle growth and differentiation
.
Curr Opin Cell Biol
.
1999
;
11
(
6
):
683
8
.
93.
Olguin
HC
,
Yang
Z
,
Tapscott
SJ
,
Olwin
BB
.
Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination
.
J Cell Biol
.
2007
;
177
(
5
):
769
79
.
94.
Onopiuk
M
,
Brutkowski
W
,
Wierzbicka
K
,
Wojciechowska
S
,
Szczepanowska
J
,
Fronk
J
,
.
Mutation in dystrophin-encoding gene affects energy metabolism in mouse myoblasts
.
Biochem Biophys Res Commun
.
2009
;
386
(
3
):
463
6
.
95.
Pant
M
,
Sopariwala
DH
,
Bal
NC
,
Lowe
J
,
Delfin
DA
,
Rafael-Fortney
J
,
.
Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy
.
PLoS One
.
2015
;
10
(
4
):
e0123875
.
96.
Peladeau
C
,
Adam
N
,
Bronicki
LM
,
Coriati
A
,
Thabet
M
,
Al-Rewashdy
H
,
.
Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles
.
Nat Commun
.
2020
;
11
(
1
):
1990
.
97.
Petrany
MJ
,
Millay
DP
.
Cell Fusion: Merging Membranes and Making Muscle
.
Trends Cell Biol
.
2019
;
29
(
12
):
964
73
.
98.
Petrillo
S
,
Pelosi
L
,
Piemonte
F
,
Travaglini
L
,
Forcina
L
,
Catteruccia
M
,
.
Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway
.
Hum Mol Genet
.
2017
;
26
(
14
):
2781
90
.
99.
Petrof
BJ
,
Shrager
JB
,
Stedman
HH
,
Kelly
AM
,
Sweeney
HL
.
Dystrophin protects the sarcolemma from stresses developed during muscle contraction
.
Proc Natl Acad Sci USA
.
1993
;
90
(
8
):
3710
4
.
100.
Phillips
HM
,
Murdoch
JN
,
Chaudhry
B
,
Copp
AJ
,
Henderson
DJ
.
Vangl2 acts via RhoA signaling to regulate polarized cell movements during development of the proximal outflow tract
.
Circ Res
.
2005
;
96
(
3
):
292
9
.
101.
Rando
TA
,
Disatnik
M-H
,
Yu
Y
,
Franco
A
.
Muscle cells from mdx mice have an increased susceptibility to oxidative stress
.
Neuromuscul Disord
.
1998
;
8
(
1
):
14
21
.
102.
Relaix
F
,
Zammit
PS
.
Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage
.
Development
.
2012
;
139
(
16
):
2845
.
103.
Rocheteau
P
,
Gayraud-Morel
B
,
Siegl-Cachedenier
I
,
Blasco
MA
,
Tajbakhsh
S
.
A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division
.
Cell
.
2012
;
148
(
1--2
):
112
25
.
104.
Romanello
V
,
Sandri
M
.
Mitochondria quality control and muscle mass maintenance
.
Front Physiol
.
2016
;
6
:
422
.
105.
Rosenberg
AS
,
Puig
M
,
Nagaraju
K
,
Hoffman
EP
,
Villalta
SA
,
Rao
VA
,
.
Immune-mediated pathology in Duchenne muscular dystrophy
.
Sci Transl Med
.
2015
;
7
(
299
):
299rv4
.
106.
Ryan
MT
,
Hoogenraad
NJ
.
Mitochondrial-nuclear communications
.
Annu Rev Biochem
.
2007
;
76
:
701
22
.
107.
Ryder
S
,
Leadley
RM
,
Armstrong
N
,
Westwood
M
,
de Kock
S
,
Butt
T
,
.
The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review
.
Orphanet J Rare Dis
.
2017
;
12
(
1
):
79
.
108.
Sacco
A
,
Mourkioti
F
,
Tran
R
,
Choi
J
,
Llewellyn
M
,
Kraft
P
,
.
Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice
.
Cell
.
2010
;
143
(
7
):
1059
71
.
109.
Salmaninejad
A
,
Valilou
SF
,
Bayat
H
,
Ebadi
N
,
Daraei
A
,
Yousefi
M
,
.
Duchenne muscular dystrophy: an updated review of common available therapies
.
Int J Neurosci
.
2018
;
128
(
9
):
854
64
.
110.
Scholte
HR
,
Busch
HFM
.
Early changes of muscle mitochondria in duchenne dystrophy: Partition and activity of mitochondrial enzymes in fractionated muscle of unaffected boys and adults and patients
.
J Neurol Sci
.
1980
;
45
(
2
):
217
34
.
111.
Seale
P
,
Sabourin
LA
,
Girgis-Gabardo
A
,
Mansouri
A
,
Gruss
P
,
Rudnicki
MA
.
Pax7 Is Required for the Specification of Myogenic Satellite Cells
.
Cell
.
2000
;
102
(
6
):
777
86
.
112.
Sharma
N
,
Medikayala
S
,
Defour
A
,
Rayavarapu
S
,
Brown
KJ
,
Hathout
Y
,
.
Use of quantitative membrane proteomics identifies a novel role of mitochondria in healing injured muscles
.
J Biol Chem
.
2012
;
287
(
36
):
30455
67
.
113.
Snijders
T
,
Nederveen
JP
,
McKay
BR
,
Joanisse
S
,
Verdijk
LB
,
van Loon
LJ
,
.
Satellite cells in human skeletal muscle plasticity
.
Front Physiol
.
2015
;
6
:
283
.
114.
Soleimani
VD
,
Punch
VG
,
Kawabe
Y
,
Jones
AE
,
Palidwor
GA
,
Porter
CJ
,
.
Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity recognition of homeodomain motifs
.
Dev Cell
.
2012
;
22
(
6
):
1208
20
.
115.
Sousa-Victor
P
,
Gutarra
S
,
Garcia-Prat
L
,
Rodriguez-Ubreva
J
,
Ortet
L
,
Ruiz-Bonilla
V
,
.
Geriatric muscle stem cells switch reversible quiescence into senescence
.
Nature
.
2014
;
506
(
7488
):
316
21
.
116.
Strassmann
G
,
Fong
M
,
Kenney
JS
,
Jacob
CO
.
Evidence for the involvement of interleukin 6 in experimental cancer cachexia
.
J Clin Invest
.
1992
;
89
(
5
):
1681
4
.
117.
Sugihara
H
,
Teramoto
N
,
Nakamura
K
,
Shiga
T
,
Shirakawa
T
,
Matsuo
M
,
.
Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy
.
Sci Rep
.
2020
;
10
(
1
):
16385
.
118.
Tierney
MT
,
Sacco
A
.
Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis
.
Trends Cell Biol
.
2016
;
26
(
6
):
434
44
.
119.
Tinsley
J
,
Potter
AC
,
Phelps
SR
,
Fisher
R
,
Trickett
JI
,
Davies
KE
.
Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene
.
Nature
.
1996
;
384
(
6607
):
349
53
.
120.
Tinsley
J
,
Deconinck
N
,
Fisher
R
,
Kahn
D
,
Phelps
S
,
Gillis
J-M
,
.
Expression of full-length utrophin prevents muscular dystrophy in mdx mice
.
Nat Med
.
1998
;
4
(
12
):
1441
4
.
121.
Tisdale
MJ
.
Mechanisms of Cancer Cachexia
.
Physiol Rev
.
2009
;
89
(
2
):
381
410
.
122.
Troy
A
,
Cadwallader
AB
,
Fedorov
Y
,
Tyner
K
,
Tanaka
KK
,
Olwin
BB
.
Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38alpha/beta MAPK
.
Cell Stem Cell
.
2012
;
11
(
4
):
541
53
.
123.
Vila
MC
,
Rayavarapu
S
,
Hogarth
MW
,
Van der Meulen
JH
,
Horn
A
,
Defour
A
,
.
Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy
.
Cell Death Differ
.
2017
;
24
(
2
):
330
42
.
124.
Wanet
A
,
Arnould
T
,
Najimi
M
,
Renard
P
.
Connecting Mitochondria, Metabolism, and Stem Cell Fate
.
Stem Cells Dev
.
2015
;
24
(
17
):
1957
71
.
125.
Wang
Y
,
Marino-Enriquez
A
,
Bennett
RR
,
Zhu
M
,
Shen
Y
,
Eilers
G
,
.
Dystrophin is a tumor suppressor in human cancers with myogenic programs
.
Nat Genet
.
2014
;
46
(
6
):
601
6
.
126.
Wang
YX
,
Feige
P
,
Brun
CE
,
Hekmatnejad
B
,
Dumont
NA
,
Renaud
JM
,
.
EGFR-Aurka Signaling Rescues Polarity and Regeneration Defects in Dystrophin-Deficient Muscle Stem Cells by Increasing Asymmetric Divisions
.
Cell Stem Cell
.
2019
;
24
(
3
):
419
32 e6
.
127.
Webster
MT
,
Manor
U
,
Lippincott-Schwartz
J
,
Fan
CM
.
Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration
.
Cell Stem Cell
.
2016
;
18
(
2
):
243
52
.
128.
Williams
G
,
Brown
T
,
Becker
L
,
Prager
M
,
Giroir
BP
.
Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes
.
Am J Physiol
.
1994
;
267
(
4 Pt 2
):
R1020
5
.
129.
Wu
Y
,
Griffin
EE
.
Regulation of Cell Polarity by PAR-1/MARK Kinase
.
Curr Top Dev Biol
.
2017
;
123
:
365
97
.
130.
Xi
H
,
Langerman
J
,
Sabri
S
,
Chien
P
,
Young
CS
,
Younesi
S
,
.
A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells
.
Cell Stem Cell
.
2020
;
27
(
1
):
1586.e10
7
.
131.
Xu
J
,
Liu
D
,
Yin
H
,
Tong
H
,
Li
S
,
Yan
Y
.
Fatty acids promote bovine skeletal muscle satellite cell differentiation by regulating ELOVL3 expression
.
Cell Tissue Res
.
2018
;
373
(
2
):
499
508
.
132.
Yablonka-Reuveni
Z
,
Anderson
JE
.
Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers
.
Dev Dyn
.
2006
;
235
(
1
):
203
12
.
133.
Yamashita
K
,
Suzuki
A
,
Satoh
Y
,
Ide
M
,
Amano
Y
,
Masuda-Hirata
M
,
.
The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b
.
Biochem Biophys Res Commun
.
2010
;
391
(
1
):
812
7
.
134.
Yin
H
,
Price
F
,
Rudnicki
MA
.
Satellite cells and the muscle stem cell niche
.
Physiol Rev
.
2013
;
93
(
1
):
23
67
.
135.
Zammit
PS
,
Relaix
F
,
Nagata
Y
,
Ruiz
AP
,
Collins
CA
,
Partridge
TA
,
.
Pax7 and myogenic progression in skeletal muscle satellite cells
.
J Cell Sci
.
2006
;
119
(
Pt 9
):
1824
32
.
136.
Zhang
H
,
Ryu
D
,
Wu
Y
,
Gariani
K
,
Wang
X
,
Luan
P
,
.
NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice
.
Science
.
2016
;
352
(
6292
):
1436
43
.
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