Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes.
Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes.
复制标题
DOI：
10.1016/j.stemcr.2014.07.012
复制
发表时间：
2014-10-14
影响因子：
5.9
通讯作者：
Metzger, Joseph M.
中科院分区：
文献类型：
--
作者：
Bedada, Fikru B.;Chan, Sunny S-K.;Metzger, Stefania K.;Zhang, Liying;Zhang, Jianyi;Garry, Daniel J.;Kamp, Timothy J.;Kyba, Michael;Metzger, Joseph M.
在干细胞领域，关于什么构成成熟心肌细胞还没有达成共识。因此，帮助形成心肌细胞成熟的分子特征将推动该领域的发展。在哺乳动物心脏中，“胎儿”TNNI基因TNNI 1（ssTnI）的失活，连同其被成人TNNI基因产物TNNI 3（cTnI）化学计量取代的时间一致性，代表了可定量的比率成熟特征。我们检查了人诱导多能干细胞（iPSC）心肌细胞（hiPSC-CM）中的TNNI同种型转变，并发现了胎儿TNNI特征，即使在长期培养期间。然而，啮齿动物干细胞衍生的和原代肌细胞转变为成人TnI谱。hiPSC-CM的急性基因工程使其能够快速转化为成熟的TnI谱。虽然没有单一的标志物来表示成熟的心肌细胞，我们建议，跟踪cTnI：ssTnI蛋白亚型的比例提供了一个有价值的成熟签名，以量化跨实验室的心肌细胞成熟状态。TNNI基因开关是hiPSC-CM的定量成熟信号，TnI同种型比率是必要的，但不是充分的，以建立成熟状态TNNI蛋白同种型转换在hiPSC-CM中停滞。基因转移使得能够在hiPSC-CM中获得成熟的TNNI标记。在这篇文章中，Metzger和他的同事表明，在人iPSC心肌细胞中，化学计量保守的TNNI亚型发育概况（hiPSC-CM）是胎儿样的，即使在长期培养期间。这项工作表明，追踪cTnI：ssTnI蛋白亚型比率可以提供成熟特征来量化心肌细胞成熟，从而能够在实验室之间进行有用的比较。
There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the “fetal” TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories. The TNNI gene switch is a quantitative maturation signal for hiPSC-CMs TnI isoform ratio is necessary, but not sufficient, to establish the mature state TNNI protein isoform switching is stalled in hiPSC-CMs Gene transfer enables acquisition of the mature TNNI signature in hiPSC-CMs In this article, Metzger and colleagues show that the stoichiometrically conserved TNNI isoform developmental profile in human iPSC cardiac myocytes (hiPSC-CMs) is fetal-like, even during long-term culture. This work shows evidence that tracking the cTnI:ssTnI protein isoform ratio can provide a maturation signature to quantify cardiac myocyte maturation, enabling useful comparisons across laboratories.
登录
查看更多内容
影响因子：
9.7
作者：
Hazeltine, Laurie B.;Badur, Mehmet G.;Lian, Xiaojun;Das, Amritava;Han, Wenqing;Palecek, Sean P.
通讯作者：
Palecek, Sean P.
影响因子：
2.1
作者：
Mourouzis I;Forini F;Pantos C;Iervasi G
通讯作者：
Iervasi G
影响因子：
37.8
作者：
Kinugawa, K;Minobe, WA;Bristow, MR
通讯作者：
Bristow, MR
影响因子：
4
作者：
Lundy, Scott D.;Zhu, Wei-Zhong;Laflamme, Michael A.
通讯作者：
Laflamme, Michael A.
影响因子：
3.7
作者：
DHOOT, GK;GELL, PGH;PERRY, SV
通讯作者：
PERRY, SV