A Versatile In Vivo System to Study Myc in Cell Reprogramming

Author(s):  
Elena Senís ◽  
Lluc Mosteiro ◽  
Dirk Grimm ◽  
María Abad
Keyword(s):  
2019 ◽  
Vol 19 (4) ◽  
pp. 248-254
Author(s):  
Marianne Lehmann ◽  
Martina Canatelli-Mallat ◽  
Priscila Chiavellini ◽  
Gloria M. Cónsole ◽  
Maria D. Gallardo ◽  
...  

Background: 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. Objective: 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. Methods: 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). Results: 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. Conclusion: 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.


2019 ◽  
Vol 19 (2) ◽  
pp. 77-90 ◽  
Author(s):  
Jin Zhou ◽  
Jie Sun

Transplantation of reprogrammed cells from accessible sources and in vivo reprogramming are potential therapies for regenerative medicine. During the last decade, genetic approaches, which mostly involved transcription factors and microRNAs, have been shown to affect cell fates. However, their potential carcinogenicity and other unexpected effects limit their translation into clinical applications. Recently, with the power of modern biology-oriented design and synthetic chemistry, as well as high-throughput screening technology, small molecules have been shown to enhance reprogramming efficiency, replace genetic factors, and help elucidate the molecular mechanisms underlying cellular plasticity and degenerative diseases. As a non-viral and non-integrating approach, small molecules not only show revolutionary capacities in generating desired exogenous cell types but also have potential as drugs that can restore tissues through repairing or reprogramming endogenous cells. Here, we focus on the recent progress made to use small molecules in cell reprogramming along with some related mechanisms to elucidate these issues.


2010 ◽  
Vol 207 (10) ◽  
pp. 2127-2140 ◽  
Author(s):  
Rachel Sarig ◽  
Noa Rivlin ◽  
Ran Brosh ◽  
Chamutal Bornstein ◽  
Iris Kamer ◽  
...  

p53 deficiency enhances the efficiency of somatic cell reprogramming to a pluripotent state. As p53 is usually mutated in human tumors and many mutated forms of p53 gain novel activities, we studied the influence of mutant p53 (mut-p53) on somatic cell reprogramming. Our data indicate a novel gain of function (GOF) property for mut-p53, which markedly enhanced the efficiency of the reprogramming process compared with p53 deficiency. Importantly, this novel activity of mut-p53 induced alterations in the characteristics of the reprogrammed cells. Although p53 knockout (KO) cells reprogrammed with only Oct4 and Sox2 maintained their pluripotent capacity in vivo, reprogrammed cells expressing mutant p53 lost this capability and gave rise to malignant tumors. This novel GOF of mut-p53 is not attributed to its effect on proliferation, as both p53 KO and mut-p53 cells displayed similar proliferation rates. In addition, we demonstrate an oncogenic activity of Klf4, as its overexpression in either p53 KO or mut-p53 cells induced aggressive tumors. Overall, our data show that reprogrammed cells with the capacity to differentiate into the three germ layers in vitro can form malignant tumors, suggesting that in genetically unstable cells, such as those in which p53 is mutated, reprogramming may result in the generation of cells with malignant tumor-forming potential.


2014 ◽  
Vol 42 (3) ◽  
pp. 711-716 ◽  
Author(s):  
Irene de Lázaro ◽  
Kostas Kostarelos

The potential of cell-replacement strategies for the treatment of disorders in which a particular cell type is damaged or degenerated has prompted the search for the perfect cell source. iPSCs (induced pluripotent stem cells) stand out as very advantageous candidates thanks to their self-renewal capacity and differentiation potential, together with the possibility of generating them from autologous somatic cells with minimally invasive techniques. However, their differentiation into the required cell type, precise delivery and successful engraftment and survival in the host are still challenging. We have proposed the transient reprogramming of somatic cells towards a pluripotent state in their in vivo microenvironment as a means to facilitate the regeneration of the tissue. The initial reports of in vivo reprogramming to pluripotency in the literature are reviewed and the potential clinical applications of this strategy are discussed.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54754 ◽  
Author(s):  
Açelya Yilmazer ◽  
Irene de Lázaro ◽  
Cyrill Bussy ◽  
Kostas Kostarelos
Keyword(s):  

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