INIBIOLP-Pathology B, Faculty of Medicine, UNLP, CC 455 (zip 1900) La Plata, Argentina.
Department of Histology, Cytology and of Embryology B, School of Medicine, University of La Plata, La Plata, Argentina.
Curr Gene Ther. 2019;19(4):248-254. doi: 10.2174/1566523219666190902154511.
Conventional cell reprogramming involves converting a somatic cell line into induced pluripotent stem cells (iPSC), which subsequently can be re-differentiated to specific somatic cell types. Alternatively, partial cell reprogramming converts somatic cells into other somatic cell types by transient expression of pluripotency genes thus generating intermediates that retain their original cell identity, but are responsive to appropriate cocktails of specific differentiation factors. Additionally, biological rejuvenation by partial cell reprogramming is an emerging avenue of research.
Here, we will briefly review the emerging information pointing to partial reprogramming as a suitable strategy to achieve cell reprogramming and rejuvenation, bypassing cell dedifferentiation.
In this context, regulatable pluripotency gene expression systems are the most widely used at present to implement partial cell reprogramming. For instance, we have constructed a regulatable bidirectional adenovector expressing Green Fluorescent Protein and oct4, sox2, klf4 and c-myc genes (known as the Yamanaka genes or OSKM).
Partial cell reprogramming has been used to reprogram fibroblasts to cardiomyocytes, neural progenitors and neural stem cells. Rejuvenation by cyclic partial reprogramming has been achieved both in vivo and in cell culture using transgenic mice and cells expressing the OSKM genes, respectively, controlled by a regulatable promoter.
Partial reprogramming emerges as a powerful tool for the genesis of iPSC-free induced somatic cells of therapeutic value and for the implementation of in vitro and in vivo rejuvenation keeping cell type identity unchanged.
传统的细胞重编程涉及将体细胞系转化为诱导多能干细胞(iPSC),然后可以将其重新分化为特定的体细胞类型。或者,通过瞬时表达多能性基因,部分细胞重编程将体细胞转化为其他体细胞类型,从而产生保留其原始细胞身份但对适当的特定分化因子鸡尾酒有反应的中间产物。此外,部分细胞重编程的生物复兴是一个新兴的研究途径。
在这里,我们将简要回顾新出现的信息,这些信息表明部分重编程是一种实现细胞重编程和复兴的合适策略,可绕过细胞去分化。
在这种情况下,可调节的多能性基因表达系统是目前最广泛使用的实现部分细胞重编程的方法。例如,我们构建了一种可调节的双向腺病毒,表达绿色荧光蛋白和 oct4、sox2、klf4 和 c-myc 基因(称为山中因子或 OSKM)。
部分细胞重编程已被用于将成纤维细胞重编程为心肌细胞、神经祖细胞和神经干细胞。使用可调节启动子分别控制表达 OSKM 基因的转基因小鼠和细胞,在体内和细胞培养中已经实现了周期性部分重编程的复兴。
部分重编程作为一种强大的工具,可用于产生无 iPSC 的诱导性治疗价值的体细胞,并实现体外和体内的复兴,同时保持细胞类型身份不变。