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Direct Cell Reprogramming: From Basic Science to Translational Medicine

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (15 May 2019) | Viewed by 26966

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Special Issue Editor

Dr. Li Qian

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Guest Editor

Department of Pathology and Laboratory Medicine, McAllister Heart Institute, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Interests: cellular reprogramming; cardiac regeneration; cell fate control; fibroblast biology; heart development; cardiovascular disease

Special Issue Information

Dear Colleagues,

Cellular reprogramming circumvents issues commonly encountered in regenerative medicine by utilizing a person’s own cells as the source of treatment. The discovery of nuclear transfer, cell fusion, and iPSC reprogramming ignited the field of direct lineage conversion. Interest in identifying and optimizing combinations of master regulators to alter cell fates has continued growing. Many research groups have successfully demonstrated direct conversions from one somatic cell type to another without going through a pluripotent or multipotent intermediate, and have applied such conversions to various disease models. In this Special Issue, we hope to cover a wide array of topics from understanding the basic science of direct cell reprogramming to their applications in organ regeneration and disease treatment.

Dr. Li Qian
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

reprogramming
cell fate
fibroblast
regeneration

Published Papers (5 papers)

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Research

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14 pages, 2390 KiB

Open AccessArticle

Isoform Specific Effects of Mef2C during Direct Cardiac Reprogramming

by Li Wang, Peisen Huang, David Near, Karan Ravi, Yangxi Xu, Jiandong Liu and Li Qian

Cells 2020, 9(2), 268; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9020268 - 22 Jan 2020

Cited by 12 | Viewed by 3357

Abstract

Direct conversion of cardiac fibroblasts into induced cardiomyocytes (iCMs) by forced expression of defined factors holds great potential for regenerative medicine by offering an alternative strategy for treatment of heart disease. Successful iCM conversion can be achieved by minimally using three transcription factors, Mef2c (M), Gata4(G), and Tbx5 (T). Despite increasing interest in iCM mechanistic studies using MGT(polycistronic construct with optimal expression of M,G and T), the reprogramming efficiency varies among different laboratories. Two main Mef2c isoforms (isoform2, Mi2 and isoform4, Mi4) are present in heart and are used separately by different labs, for iCM reprogramming. It is currently unknown if differently spliced isoform of Mef2c contributes to varied reprogramming efficiency. Here, we used Mi2 and Mi4 together with Gata4 and Tbx5 in separate vectors or polycistronic vector, to convert fibroblasts to iCMs. We found that Mi2 can induce higher reprogramming efficiency than Mi4 in MEFs. Addition of Hand2 to MGT retroviral cocktail or polycistronic Mi2-GT retroviruses further enhanced the iCM conversion. Overall, this study demonstrated the isoform specific effects of Mef2c, during iCM reprogramming, clarified some discrepancy about varied efficiency among labs and might lead to future research into the role of alternative splicing and the consequent variants in cell fate determination. Full article

(This article belongs to the Special Issue Direct Cell Reprogramming: From Basic Science to Translational Medicine)

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17 pages, 5540 KiB

Open AccessArticle

Inhibition of Glioma Development by ASCL1-Mediated Direct Neuronal Reprogramming

by Xueyan Cheng, Zijian Tan, Xiao Huang, Yimin Yuan, Shangyao Qin, Yakun Gu, Dan Wang, Cheng He and Zhida Su

Cells 2019, 8(6), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8060571 - 11 Jun 2019

Cited by 17 | Viewed by 5042

Abstract

Direct conversion of non-neural cells into induced neurons holds great promise for brain repair. As the most common malignant tumor in the central nervous system, glioma is currently incurable due to its exponential growth and invasive behavior. Given that neurons are irreversible postmitotic cells, reprogramming glioma cells into terminally differentiated neuron-like cells represents a potential approach to inhibit brain tumor development. We here show that human glioma cells can be directly, rapidly and efficiently reprogrammed into terminally differentiated neuron-like cells by the single transcription factor ASCL1 (Achaete-scute complex-like 1, also known as MASH1). These induced cells exhibit typical neuron-like morphology and express multiple neuron-specific markers. Importantly, ASCL1-mediated neuronal reprogramming drives human glioma cells to exit the cell cycle and results in dramatic inhibition of proliferation, both in vitro and in vivo. Taken together, this proof-of-principle study demonstrates a potential strategy for impeding brain tumor development by ASCL1-induced direct neuronal reprogramming. Full article

(This article belongs to the Special Issue Direct Cell Reprogramming: From Basic Science to Translational Medicine)

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Review

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16 pages, 2253 KiB

Open AccessReview

Experimental and Computational Approaches to Direct Cell Reprogramming: Recent Advancement and Future Challenges

by Rihab Gam, Minkyung Sung and Arun Prasad Pandurangan

Cells 2019, 8(10), 1189; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8101189 - 2 Oct 2019

Cited by 7 | Viewed by 6186

Abstract

The process of direct cell reprogramming, also named transdifferentiation, permits for the conversion of one mature cell type directly into another, without returning to a dedifferentiated state. This makes direct reprogramming a promising approach for the development of several cellular and tissue engineering therapies. To achieve the change in the cell identity, direct reprogramming requires an arsenal of tools that combine experimental and computational techniques. In the recent years, several methods of transdifferentiation have been developed. In this review, we will introduce the concept of direct cell reprogramming and its background, and cover the recent developments in the experimental and computational prediction techniques with their applications. We also discuss the challenges of translating this technology to clinical setting, accompanied with potential solutions. Full article

(This article belongs to the Special Issue Direct Cell Reprogramming: From Basic Science to Translational Medicine)

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25 pages, 998 KiB

Open AccessReview

The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

by Michele d’Angelo, Elisabetta Benedetti, Maria Grazia Tupone, Mariano Catanesi, Vanessa Castelli, Andrea Antonosante and Annamaria Cimini

Cells 2019, 8(9), 1036; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8091036 - 5 Sep 2019

Cited by 71 | Viewed by 7238

Abstract

The mechanotransduction is the process by which cells sense mechanical stimuli such as elasticity, viscosity, and nanotopography of extracellular matrix and translate them into biochemical signals. The mechanotransduction regulates several aspects of the cell behavior, including migration, proliferation, and differentiation in a time-dependent manner. Several reports have indicated that cell behavior and fate are not transmitted by a single signal, but rather by an intricate network of many signals operating on different length and timescales that determine cell fate. Since cell biology and biomaterial technology are fundamentals in cell-based regenerative therapies, comprehending the interaction between cells and biomaterials may allow the design of new biomaterials for clinical therapeutic applications in tissue regeneration. In this work, we present the most relevant mechanism by which the biomechanical properties of extracellular matrix (ECM) influence cell reprogramming, with particular attention on the new technologies and materials engineering, in which are taken into account not only the biochemical and biophysical signals patterns but also the factor time. Full article

(This article belongs to the Special Issue Direct Cell Reprogramming: From Basic Science to Translational Medicine)

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16 pages, 1770 KiB

Open AccessReview

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

by Emre Bektik and Ji-dong Fu

Cells 2019, 8(7), 679; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8070679 - 4 Jul 2019

Cited by 20 | Viewed by 4621

Abstract

Coronary artery disease is the most common form of cardiovascular diseases, resulting in the loss of cardiomyocytes (CM) at the site of ischemic injury. To compensate for the loss of CMs, cardiac fibroblasts quickly respond to injury and initiate cardiac remodeling in an injured heart. In the remodeling process, cardiac fibroblasts proliferate and differentiate into myofibroblasts, which secrete extracellular matrix to support the intact structure of the heart, and eventually differentiate into matrifibrocytes to form chronic scar tissue. Discovery of direct cardiac reprogramming offers a promising therapeutic strategy to prevent/attenuate this pathologic remodeling and replace the cardiac fibrotic scar with myocardium in situ. Since the first discovery in 2010, many progresses have been made to improve the efficiency and efficacy of reprogramming by understanding the mechanisms and signaling pathways that are activated during direct cardiac reprogramming. Here, we overview the development and recent progresses of direct cardiac reprogramming and discuss future directions in order to translate this promising technology into an effective therapeutic paradigm to reverse cardiac pathological remodeling in an injured heart. Full article

(This article belongs to the Special Issue Direct Cell Reprogramming: From Basic Science to Translational Medicine)

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