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体外获得ips细胞源性isl心脏祖细胞# O0 V; K9 G% M1 j6 h' a$ L0 C
Mouse and human induced pluripotent stem cells as a$ S* R/ |/ i5 `# n# `# P
source for multipotent Isl1 cardiovascular; f- K# L/ i- J8 z9 q. f5 z: W
progenitors
3 c+ G) z) O4 p" f7 A# \Alessandra Moretti,*,1 Milena Bellin,*,1 Christian B. Jung,*,1 Tu-Mai Thies,*
& F# i8 Q0 \8 z" K+ ZYasuhiro Takashima,§ Alexandra Bernshausen,* Matthias Schiemann,† Stefanie Fischer,‡) e3 _/ H% L. Y8 r/ N' L' O& w0 O
Sven Moosmang,‡ Austin G. Smith,§ Jason T. Lam,*,2 and Karl-Ludwig Laugwitz*,2/ P+ i+ O% `6 _3 p
*Klinikum rechts der Isar and Deutsches Herzzentrum, Medical Department, Molecular Cardiology, i: G8 a! D% d
†Institute of Medical Microbiology, Immunology, and Hygiene, and ‡Institute of Pharmacology,
5 B9 Y$ P: n* R6 g$ jTechnical University of Munich, Munich, Germany; and §Wellcome Trust Centre for Stem Cell Research,
+ x0 ^- U2 l4 ?( }; ^University of Cambridge, Cambridge, UK
6 L) F& h- o8 ` t, s* d, ?9 DABSTRACT Ectopic expression of defined sets of. H8 Z! I$ [" U" e7 A' w% S
genetic factors can reprogram somatic cells to create
5 @0 m+ n7 O+ p0 Finduced pluripotent stem (iPS) cells. The capacity to
; w4 [* ` k) `- q8 adirect human iPS cells to specific differentiated lineages/ l' p4 _7 B6 g- X' h W
and to their progenitor populations can be used6 y2 Y& g U+ ?1 {: ?) M
for disease modeling, drug discovery, and eventually+ Y: {) C' a& O. I; n8 E/ x
autologous cell replacement therapies. During mouse) F. c5 H. n( _- @+ y
cardiogenesis, the major lineages of the mature heart,$ `! u4 M3 H& f8 G1 h3 ~
cardiomyocytes, smooth muscle cells, and endothelial/ }8 C2 ~$ h2 r! a s7 e% `
cells arise from a common, multipotent cardiovascular
5 q% v% P" v Y9 q- }9 nprogenitor expressing the transcription factors Isl1 and. v8 @* I L7 b
Nkx2.5. Here we show, using genetic fate-mapping, that
' T; q& |# ]; p& d7 ?/ tIsl1 multipotent cardiovascular progenitors can be generated
- m% d& d0 @) yfrom mouse iPS cells and spontaneously differentiate
; V0 a& C! G/ C: Jin all 3 cardiovascular lineages in vivo without teratoma.
/ [6 _" G6 k/ U- G$ n/ dMoreover, we report the identification of human
0 h' e8 K2 `8 W0 W, a/ yiPS-derived ISL1 progenitors with similar developmental% R& t! i, _* P4 m2 D
potential. These results support the possibility to use
7 t! h3 |2 }& z" Upatient-specific iPS-generated cardiovascular progenitors
?7 J C. } S: g- x4 t- has a model to elucidate the pathogenesis of congenital and% O g; r$ w; P4 k7 n
acquired forms of heart diseases.—Moretti, A., Bellin,8 l, a$ _2 U3 c1 X5 w# Y; ^1 v- S
M., Jung, C. B., Thies, T.-M., Takashima, Y., Bernshausen,
# O$ v- D! P1 K4 M+ H6 D. A% {9 qA., Schiemann, M., Fischer, S., Moosmang, S., Smith, A., n# m5 }5 |. Z8 F3 _0 _# o. i
G., Lam, J. T., Laugwitz, K.-L. Mouse and human
7 n1 h0 ?& V2 V) ainduced pluripotent stem cells as a source for multipotent
]. ]. N6 T5 U* WIsl1 cardiovascular progenitors. FASEB J. 24,$ u: }4 r& D, f$ b. ]
000–000 (2010). www.fasebj.org |
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发表于 2010-5-7 10:33
