Cellular Reprogramming and Fate Conversion

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

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Integrated multi-omics analysis of RB-loss identifies widespread cellular programming and synthetic weaknesses

Communications Biology ◽

10.1038/s42003-021-02495-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Swetha Rajasekaran ◽

Jalal Siddiqui ◽

Jessica Rakijas ◽

Brandon Nicolay ◽

Chenyu Lin ◽

...

Keyword(s):

Metabolic Pathways ◽

Human Cells ◽

Cellular Reprogramming ◽

Hallmarks Of Cancer ◽

Compensatory Mechanisms ◽

Response Factors ◽

Cancer Data ◽

Cell Stress Response ◽

Metabolic Output

AbstractInactivation of RB is one of the hallmarks of cancer, however gaps remain in our understanding of how RB-loss changes human cells. Here we show that pRB-depletion results in cellular reprogramming, we quantitatively measured how RB-depletion altered the transcriptional, proteomic and metabolic output of non-tumorigenic RPE1 human cells. These profiles identified widespread changes in metabolic and cell stress response factors previously linked to E2F function. In addition, we find a number of additional pathways that are sensitive to RB-depletion that are not E2F-regulated that may represent compensatory mechanisms to support the growth of RB-depleted cells. To determine whether these molecular changes are also present in RB1−/− tumors, we compared these results to Retinoblastoma and Small Cell Lung Cancer data, and identified widespread conservation of alterations found in RPE1 cells. To define which of these changes contribute to the growth of cells with de-regulated E2F activity, we assayed how inhibiting or depleting these proteins affected the growth of RB1−/− cells and of Drosophila E2f1-RNAi models in vivo. From this analysis, we identify key metabolic pathways that are essential for the growth of pRB-deleted human cells.

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Epigenetic Mechanisms in Cellular Reprogramming. Epigenetics and Human Health. Edited by Alexander Meissner and Jörn Walter. Heidelberg (Germany) and New York: Springer. $189.00. xviii + 230 p.; ill.; index. ISBN: 978-3-642-31973-0 (hc); 978-3-642-31974-7 (eb). 2015.

The Quarterly Review of Biology ◽

10.1086/690888 ◽

2017 ◽

Vol 92 (1) ◽

pp. 108-108

Keyword(s):

New York ◽

Human Health ◽

Cellular Reprogramming ◽

Epigenetic Mechanisms

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A Review on Electroporation-Based Intracellular Delivery

Molecules ◽

10.3390/molecules23113044 ◽

2018 ◽

Vol 23 (11) ◽

pp. 3044 ◽

Cited By ~ 44

Author(s):

Junfeng Shi ◽

Yifan Ma ◽

Jing Zhu ◽

Yuanxin Chen ◽

Yating Sun ◽

...

Keyword(s):

Viral Vectors ◽

Safety Issue ◽

Intracellular Delivery ◽

Cellular Reprogramming ◽

Gene Therapies ◽

Potential Safety ◽

Potential Applications ◽

Dose Control ◽

Intracellular Probe ◽

New Generation

Intracellular delivery is a critical step in biological discoveries and has been widely utilized in biomedical research. A variety of molecular tools have been developed for cell-based gene therapies, including FDA approved CAR-T immunotherapy, iPSC, cell reprogramming and gene editing. Despite the inspiring results of these applications, intracellular delivery of foreign molecules including nucleic acids and proteins remains challenging. Efficient yet non-invasive delivery of biomolecules in a high-throughput manner has thus long fascinates the scientific community. As one of the most popular non-viral technologies for cell transfection, electroporation has gone through enormous development with the assist of nanotechnology and microfabrication. Emergence of miniatured electroporation system brought up many merits over the weakness of traditional electroporation system, including precise dose control and high cell viability. These new generation of electroporation systems are of considerable importance to expand the biological applications of intracellular delivery, bypassing the potential safety issue of viral vectors. In this review, we will go over the recent progresses in the electroporation-based intracellular delivery and several potential applications of cutting-edge research on the miniatured electroporation, including gene therapy, cellular reprogramming and intracellular probe.

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