Nuclear reprogramming strategy modulates differentiation potential of induced pluripotent stem cells.
Nuclear reprogramming strategy modulates differentiation potential of induced pluripotent stem cells.
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DOI：
10.1007/s12265-010-9250-2
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发表时间：
2011-04
影响因子：
3.4
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Martinez-Fernandez, Almudena;Nelson, Timothy J.;Terzic, Andre
通过干细胞因子的异位表达进行生物工程化，诱导多能干（iPS）细胞显示出胚胎干细胞样特性，并为从体组织来源衍生自体多能细胞提供了独特的平台。在核重编程的过程中，体细胞组织被转化为多能基态，从而释放出无限的潜力来扩大祖细胞库。核重编程的分子解剖表明，源自原始亲本来源的残余记忆，沿着重编程过程本身的残余，导致生物工程后代分化成靶组织如心脏细胞型的偏向潜力。以这种方式，满足多能性标准的iPS细胞可以显示谱系特化的异质谱。已经确定了基于小分子的策略，其调节重编程细胞的表观遗传状态，并被优化以擦除残留记忆并使来自不同背景的iPS细胞的分化潜能均质化。在这里，我们描述的重编程过程的显着组成部分，其对下游分化能力的iPS人口的背景下，心血管再生应用的影响。
Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stem cell-like properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited potential to expand progenitor pools. Molecular dissection of nuclear reprogramming suggests that a residual memory derived from the original parental source, along with the remnants of the reprogramming process itself, leads to a biased potential of the bioengineered progeny to differentiate into target tissues such as cardiac cytotypes. In this way, iPS cells that fulfill pluripotency criteria may display heterogeneous profiles for lineage specification. Small molecule-based strategies have been identified that modulate the epigenetic state of reprogrammed cells and are optimized to erase the residual memory and homogenize the differentiation potential of iPS cells derived from distinct backgrounds. Here, we describe the salient components of the reprogramming process and their effect on the downstream differentiation capacity of the iPS populations in the context of cardiovascular regenerative applications.
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