Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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.

SUBMITTER: Gam R

PROVIDER: S-EPMC6829265 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Gam Rihab R Sung Minkyung M Prasad Pandurangan Arun A

Cells 20191002 10

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, severa ...[more]

PMID: 31581647

Similar Datasets

Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.

Project description:The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

| S-EPMC6131668 | biostudies-other

Multilevel developmental approaches to understanding the effects of child maltreatment: Recent advances and future challenges.

Project description:Recent research in the field of child maltreatment has begun to shed new light on the emergence of health problems in children by emphasizing the responsiveness of developmental processes to children's environmental and biological contexts. Here, I highlight recent trends in the field with an emphasis on the effects of early life stress across multiple levels of developmental domains.

| S-EPMC4832417 | biostudies-literature

Epigenetic Reprogramming During Somatic Cell Nuclear Transfer: Recent Progress and Future Directions.

Project description:Somatic cell nuclear transfer (SCNT) has broad applications but is limited by low cloning efficiency. In this review, we mainly focus on SCNT-mediated epigenetic reprogramming in livestock and also describe mice data for reference. This review presents the factors contributing to low cloning efficiency, demonstrates that incomplete epigenetic reprogramming leads to the low developmental potential of cloned embryos, and further describes the regulation of epigenetic reprogramming by long non-coding RNAs, which is a new research perspective in the field of SCNT-mediated epigenetic reprogramming. In conclusion, this review provides new insights into the epigenetic regulatory mechanism during SCNT-mediated nuclear reprogramming, which could have great implications for improving cloning efficiency.

| S-EPMC7093498 | biostudies-literature

Purging disorder: recent advances and future challenges.

Project description:PURPOSE OF REVIEW:The present review aims to help specialists remain up-to-date on research from the past 2 years on epidemiology, risk factors, biological correlates, treatment, and outcomes for purging disorder, a DSM-5 other specified feeding and eating disorder. RECENT FINDINGS:Purging disorder affects 2.5-4.8% of adolescent females in population-based samples, but purging disorder remains relatively rare in treatment settings. Higher premorbid body mass index, body dissatisfaction, and dieting prospectively predict purging disorder onset. In studies of biological correlates, women with purging disorder demonstrated significantly greater postprandial increases in the satiety peptide, peptide tyrosine tyrosine, compared to women with bulimia nervosa and controls, and these differences predicted greater gastrointestinal distress in purging disorder. Less than half of those with purging disorder are free from an eating disorder at the end of treatment and at one or more years of follow-up, supporting the need for improved interventions. SUMMARY:Purging disorder may occupy a space that falls between anorexia and bulimia nervosa, making it 'not quite' anorexia and 'not quite' bulimia and difficult to reliably distinguish from each. Improved recognition and understanding of purging disorder requires more research specifically designed to test models of risk and maintenance factors to advance interventions for those who purge without binge eating.

| S-EPMC6768735 | biostudies-literature

Computational approaches for predicting key transcription factors in targeted cell reprogramming (Review).

Project description:There is a need for specific cell types in regenerative medicine and biological research. Frequently, specific cell types may not be easily obtained or the quantity obtained is insufficient for study. Therefore, reprogramming by the direct conversion (transdifferentiation) or re‑induction of induced pluripotent stem cells has been used to obtain cells expressing similar profiles to those of the desired types. Therefore, a specific cocktail of transcription factors (TFs) is required for induction. Nevertheless, identifying the correct combination of TFs is difficult. Although certain computational approaches have been proposed for this task, their methods are complex, and corresponding implementations are difficult to use and generalize for specific source or target cell types. In the present review four computational approaches that have been proposed to obtain likely TFs were compared and discussed. A simplified view of the computational complexity of these methods is provided that consists of three basic ideas: i) The definition of target and non‑target cell types; ii) the estimation of candidate TFs; and iii) filtering candidates. This simplified view was validated by analyzing a well‑documented cardiomyocyte differentiation. Subsequently, these reviewed methods were compared when applied to an unknown differentiation of corneal endothelial cells. The generated results may provide important insights for laboratory assays. Data and computer scripts that may assist with direct conversions in other cell types are also provided.

| S-EPMC6072137 | biostudies-literature

CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges.

Project description:In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T-cell therapy for glioblastoma. In addition, despite formidable barriers to T-cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T-cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.

| S-EPMC6176794 | biostudies-literature

Immunotherapy for prostate cancer: recent developments and future challenges.

Project description:Since the approval of sipuleucel-T for men with metastatic castrate resistant prostate cancer in 2010, great strides in the development of anti-cancer immunotherapies have been made. Current drug development in this area has focused primarily on antigen-specific (i.e. cancer vaccines and antibody based therapies) or checkpoint inhibitor therapies, with the checkpoint inhibitors perhaps gaining the most attention as of late. Indeed, drugs blocking the inhibitory signal generated by the engagement of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) found on T-cells has emerged as potent means to combat the immunosuppressive milieu. The anti-CTLA-4 monoclonal antibody ipilimumab has already been approved in advanced melanoma and two phase III trials evaluating ipilimumab in men with metastatic castrate-resistant prostate cancer are underway. A phase III trial evaluating ProstVac-VF, a poxvirus-based therapeutic prostate cancer vaccine, is also underway. While there has been reason for encouragement over the past few years, many questions regarding the use of immunotherapies remain. Namely, it is unclear what stage of disease is most likely to benefit from these approaches, how best to incorporate said treatments with each other and into our current treatment regimens and which therapy is most appropriate for which disease. Herein we review some of the recent advances in immunotherapy as related to the treatment of prostate cancer and outline some of the challenges that lie ahead.

| S-EPMC4116461 | biostudies-literature

Recent advances in theranostics and challenges for the future.

Project description:Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging. However, the retrospective uncontrolled data currently available are inadmissible for formal regulatory agency evaluation. The challenge is to engage with oncologists and urologists, and to collaborate with the pharmaceutical industry, to design and perform the controlled clinical trials required for regulatory approval, and eventual reimbursement for theranostic nuclear oncology procedures. Strategies to facilitate timely establishment of an evidence base are considered in this review of theranostic advances over the past year. The prime objective is the provision of novel, effective, safe, personalised, tumour-targeted molecular theranostic management of metastatic castrate-resistant prostate cancer, and other cancers, such as non-Hodgkin lymphoma, which express the appropriate molecular receptor tumour targets. It would also be desirable to offer theranostic treatments at an earlier stage of malignant disease when the benefit is likely to be greater. The ultimate goal of theranostic nuclear oncology is to prolong survival and to improve quality of life for cancer patients worldwide. This may only be achieved through close collaboration between oncologists, nuclear physicians, radiologists, dosimetric physicists, Pharma, and, above all, with the patients themselves, in ways which are explored in this review.

| S-EPMC6475948 | biostudies-literature

Computational Approaches and Challenges to Developing Universal Influenza Vaccines.

Project description:The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.

| S-EPMC6631137 | biostudies-literature

Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges.

Project description:Islet transplantation is a well-established therapeutic treatment for a subset of patients with complicated type I diabetes mellitus. Prior to the Edmonton Protocol, only 9% of the 267 islet transplant recipients since 1999 were insulin independent for >1 year. In 2000, the Edmonton group reported the achievement of insulin independence in seven consecutive patients, which in a collaborative team effort propagated expansion of clinical islet transplantation centers worldwide in an effort to ameliorate the consequences of this disease. To date, clinical islet transplantation has established improved success with insulin independence rates up to 5 years post-transplant with minimal complications. In spite of marked clinical success, donor availability and selection, engraftment, and side effects of immunosuppression remain as existing obstacles to be addressed to further improve this therapy. Clinical trials to improve engraftment, the availability of insulin-producing cell sources, as well as alternative transplant sites are currently under investigation to expand treatment. With ongoing experimental and clinical studies, islet transplantation continues to be an exciting and attractive therapy to treat type I diabetes mellitus with the prospect of shifting from a treatment for some to a cure for all.

| S-EPMC4075233 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data