Delayed onset of beating and decreased expression of T-type Ca2+ channel in mouse ES cell-derived cardiocytes carrying human chromosome 21.
The mouse ES cell line hcgp7/#21, which carries a human chromosome 21 (hChr.21), was used as an in vitro model to examine the effects of hChr.21 on cardiomyocyte differentiation. Cardiomyocytes derived from hcgp7/#21 showed a significant delay in the onset of spontaneous beating. The number of Nkx2.5/GFP(+) cardiac progenitor cells was comparable to that in control ES cells and they also expressed comparable mRNA levels for mesodermal markers, cardiac specific transcription factors, contractile proteins, and L-type Ca(2+) channels. However, cells from hcgp7/#21 expressed significantly reduced levels of mRNA for Cav3.1 and Cav3.2, which was consistent with the decreased number of cells expressing T-type Ca(2+) channels and decreased T-type Ca(2+) channel currents. These findings suggest that the presence of human chromosome 21 suppresses expression of T-type Ca(2+) channels in cardiomyocytes during differentiation, which may be responsible for delayed onset of spontaneous beating.
Mizuta
Einosuke
E
Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science, 86 Nishi-cho, Yonago 683-8503, Japan. einosuke@ri.ncvc.go.jp
Furuichi
Hitomi
H
Kazuki
Yasuhiro
Y
Miake
Junichiro
J
Yano
Shuichi
S
Bahrudin
Udin
U
Yamamoto
Yasutaka
Y
Igawa
Osamu
O
Shigemasa
Chiaki
C
Hidaka
Kyoko
K
Morisaki
Takayuki
T
Kurata
Yasutaka
Y
Ninomiya
Haruaki
H
Kitakaze
Masafumi
M
Shirayoshi
Yasuaki
Y
Oshimura
Mitsuo
M
Hisatome
Ichiro
I
D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D013997:Time Factors
D020747:Calcium Channels, T-Type