Direct reprogramming of adult cells: avoiding the pluripotent state

Kelaini, Sophia; Cochrane, Amy; Margariti, Andriana

doi:10.2147/sccaa.s38006

Cited by 50 publications

(47 citation statements)

References 102 publications

(159 reference statements)

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“…Induced pluripotent stem (iPS) cells can now be derived from a wide range of somatic cells via the over-expression of a cocktail of TFs [6] or a combination of TF expression with chemical compounds [7, 8]. Moreover, somatic cells can now be directly reprogrammed into entirely different cell types [9] through the expression of lineage-specific sets of transcription factors. Yamanaka's seminal discovery has introduced the concept that the fate of adult somatic cells can be controlled through TF expression.…”

Section: Introductionmentioning

confidence: 99%

Stemness-related markers in cancer

2017

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Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute towards a ‘stemness’ phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers and signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Stemness-related markers in cancer

2017

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“…10 Interest is now focused on converting cell fates without going through a pluripotent intermediate. 11–13 Multiple studies have demonstrated our ability to directly convert fibroblasts to other cell types, such as functional/spinal motor neurons, myelinogenic oligodendrocyte progenitor cells, neural stem cells, cardiomyocytes, striated mononucleated myoblasts, multinucleated myotubes, Sertoli cells, macrophages, and hepatocyte-like cells 14–24 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Daniel¹,

Lemischka

Moore³

2016

Annals of the New York Academy of Sciences

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Even though all paradigms of stem cell therapy and regenerative medicine emerged from the study of hematopoietic stem cells (HSCs), our inability to generate these cells de novo or expand them in vitro persists. Initial efforts to obtain these cells began with the use of embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technologies, but these strategies have yet to yield fully functional cells. Subsequently, more recent approaches involve transcription factor (TF) overexpression to reprogram PSCs and various somatic cells. The induction of pluripotency with just four TFs by Shinya Yamanaka informs our ability to convert cell fates, and demonstrates the feasibility of utilizing terminally differentiated cells to generate cells with multilineage potential. In this review, we discuss the recent efforts undertaken using TF-based reprogramming strategies to convert several cell types into HSCs.

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“…The transdifferentiation process takes shorter time compared to iPSC generation 23 . Direct reprogramming is, therefore, a viable option for cell derivation in regenerative and personalized medicine application.…”

Section: Discussionmentioning

confidence: 99%

Bioreactor model of neuromuscular junction with electrical stimulation for pharmacological potency testing

et al. 2017

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In vitro models of the neuromuscular junction (NMJ) are emerging as a valuable tool to study synaptogenesis, synaptic maintenance, and pathogenesis of neurodegenerative diseases. Many models have previously been developed using a variety of cell sources for skeletal muscle and motoneurons. These models can advanced by integrating beneficial features of the native developmental milieu of the NMJ. We created a functional in vitro model of NMJ by bioreactor cultivation of transdifferentiated myocytes and stem cell-derived motoneurons, in the presence of electrical stimulation. In conjunction with a coculture medium, electrical stimulation resulted in improved maturation and function of motoneurons and myocytes, as evidenced by mature cellular structures, increased expression of neuronal and muscular genes, clusterization of acetylcholine receptors (AChRs) in the vicinity of motoneurons, and the response to glutamate stimulation. To validate the model and demonstrate its utility for pharmacological testing, we documented the potency of drugs that affect key pathways during NMJ signal transduction: (i) acetylcholine (ACh) synthesis, (ii) ACh vesicular storage, (iii) ACh synaptic release, (iv) AChR activation, and (v) ACh inactivation in the synaptic cleft. The model properly responded to the drugs in a concentration-dependent manner. We thus propose that this in vitro model of NMJ could be used as a platform in pharmacological screening and controlled studies of neuromuscular diseases.

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Direct reprogramming of adult cells: avoiding the pluripotent state

Cited by 50 publications

References 102 publications

Stemness-related markers in cancer

Stemness-related markers in cancer

Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming

Bioreactor model of neuromuscular junction with electrical stimulation for pharmacological potency testing

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