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Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency before establishing the neural fate. We employed genetic lineage tracing and found that induction of iNSCs with individual vectors leads to direct lineage conversion. In contrast, polycistronic expression produces a Brn4-Klf4 fusion protein that enables induction of pluripotency. Our study demonstrates that a combination of pluripotency and tissue-specific factors allows direct somatic cell transdifferentiation, bypassing the acquisition of a pluripotent state. This result has major implications for lineage conversion technologies, which hold potential for providing a safer alternative to iPSCs for clinical application both in vitro and in vivo.
This article was published in the following journal.
Name: Cell reports
The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems ar...
Remodeling of the gene regulatory network in cells is believed to be a prerequisite for their lineage reprogramming. However, its key regulatory factors are not yet elucidated. In this paper we invest...
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at sing...
Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metaboli...
Currently, much effort is directed towards the development of new cell sources for clinical therapy using cell fate conversion approaches by small molecules. Direct lineage reprogramming to a progenit...
This study investigates the reprogramming of myeloid cells in patients with thyroid carcinoma. The investigators hypothesize that tumor-derived factors change the function of myeloid cells...
The purpose of this study is to investigate whether reprogramming the microbiome via soluble fiber supplementation will decrease liver fat in obese individuals.
The purpose of this study is to evaluate the effectiveness of a new cognitive behavioural therapy (CBT) group for individuals with a somatic symptom disorder (i.e., Somatic Symptom and Rel...
Patients diagnosed with chronic SIJ pain that can be treated by sacroiliac joint fusion or radiofrequency ablation. The radio frequency ablation is performed using either conventional or "...
Neurological and neurodegenerative diseases have a major impact in families and in the national health service due to the lack in many cases of effective and long-lasting therapies. The la...
The process that reverts CELL NUCLEI of fully differentiated somatic cells to a pluripotent or totipotent state. This process can be achieved to a certain extent by NUCLEAR TRANSFER TECHNIQUES, such as fusing somatic cell nuclei with enucleated pluripotent embryonic stem cells or enucleated totipotent oocytes. GENE EXPRESSION PROFILING of the fused hybrid cells is used to determine the degree of reprogramming. Dramatic results of nuclear reprogramming include the generation of cloned mammals, such as Dolly the sheep in 1997.
Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization.
Procedures used for the induction of CELLULAR REPROGRAMMING to change the terminal phenotype of a cell, such as the generation of INDUCED PLURIPOTENT STEM CELLS from differentiated adult cells by the forced expression of specific genes.
Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.
The GENETIC RECOMBINATION of the parts of two or more GENES resulting in a gene with different or additional regulatory regions, or a new chimeric gene product. ONCOGENE FUSION includes an ONCOGENE as at least one of the fusion partners and such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS. ARTIFICIAL GENE FUSION is carried out in vitro by RECOMBINANT DNA technology.
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...
Track and monitor developments in stem cell research and commercial development. Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry. BioPort...
Mergers & Acquisitions
Commercial and market reports on mergers and acquisitions in the biotechnology, pharmaceutical, medical device and life-science industries. Mergers and acquisitions (abbreviated M&A;) is an aspect of corporate strategy, corporate finance and manageme...