Direct conversion of human fibroblasts to multilineage blood progenitors

Szabó, Éva; Rampalli, Shravanti; Risueño, Ruth M.; Schnerch, Angelique; Mitchell, Ryan R.; Fiebig‐Comyn, Aline; Levadoux-Martin, Marilyne; Bhatia, Mickie

doi:10.1038/nature09591

Cited by 653 publications

(551 citation statements)

References 46 publications

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“…This is reflected in the difficulty to generate bona fide HSCs de novo from ES/iPS cells [50,85,[91][92][93], or through direct reprogramming [94,95]. This indicates that critical components of EHT, responsible for regulating the hematopoietic nature of these cells are missing in these culture systems and indicate the importance of understanding the cellular, molecular and niche requirements for EHT in vivo.…”

Section: Discussionmentioning

confidence: 99%

A short history of hemogenic endothelium

Swiers

Rode

Azzoni

et al. 2013

Blood Cells, Molecules, and Diseases

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Definitive hematopoietic cells are generated de novo during ontogeny from a specialized subset of endothelium, the so-called hemogenic endothelium. In this review we give a brief overview of the identification of hemogenic endothelium, explore its links with the HSC lineage, and summarize recent insights into the nature of hemogenic endothelium and the microenvironmental and intrinsic regulators contributing to its transition into blood. Ultimately, a better understanding of the processes controlling the transition of endothelium into blood will advance the generation and expansion of hematopoietic stem cells for therapeutic purposes.

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Section: Discussionmentioning

confidence: 99%

A short history of hemogenic endothelium

Swiers

Rode

Azzoni

et al. 2013

Blood Cells, Molecules, and Diseases

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“…Recent reprogramming reviews cover the historic events that led to the iPS cell reprogramming strategy, improved reprogramming methods and disease modeling with iPS cells in depth [35,36]. Notably, new reprogramming methods that convert one differentiated cell into another, without establishing an intermediate pluripotent state (lineage conversion) [37][38][39], point us to alternative approaches of induced cell fate change that we will discuss at the end.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

2011

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In 2006, the "wall came down" that limited the experimental conversion of differentiated cells into the pluripotent state. In a landmark report, Shinya Yamanaka's group described that a handful of transcription factors (Oct4, Sox2, Klf4 and c-Myc) can convert a differentiated cell back to pluripotency over the course of a few weeks, thus reprograming them into induced pluripotent stem (iPS) cells. The birth of iPS cells started off a rush among researchers to increase the efficiency of the reprogramming process, to reveal the underlying mechanistic events, and allowed the generation of patient-and disease-specific human iPS cells, which have the potential to be converted into relevant specialized cell types for replacement therapies and disease modeling. This review addresses the steps involved in resetting the epigenetic landscape during reprogramming. Apparently, defined events occur during the course of the reprogramming process. Immediately, upon expression of the reprogramming factors, some cells start to divide faster and quickly begin to lose their differentiated cell characteristics with robust downregulation of somatic genes. Only a subset of cells continue to upregulate the embryonic expression program, and finally, pluripotency genes are upregulated establishing an embryonic stem cell-like transcriptome and epigenome with pluripotent capabilities. Understanding reprogramming to pluripotency will inform mechanistic studies of lineage switching, in which differentiated cells from one lineage can be directly reprogrammed into another without going through a pluripotent intermediate.

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“…To date, fibroblasts have been successfully converted into neuronal cells 61 and multilineage blood progenitors. 62 CMC-like cells have also been obtained by ectopic expression of the cardiac-specific genes Gata4, Mef2c and Tbx5. 63 Even though further studies are necessary to determine the molecular and functional properties of the converted cells, transdifferentiation may represent a valid alternative for the generation of patient-specific differentiated cells and the production of CMCs for modelling and therapy of cardiovascular disease.…”

Section: Reprogramming Strategies: a Peek At Disease Mechanisms Whilementioning

confidence: 99%

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function

et al. 2012

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Engineered recombinant viral vectors are a powerful tool for vehiculating genetic information into mammalian cells. Because of their ability to infect both dividing and non-dividing cells with high efficiency, lentiviral vectors have gained particular interest for basic research and preclinical studies in the cardiovascular field. We review here the major applications for lentiviral-vector technology in the cardiovascular field: we will discuss their use in trailing gene expression during the induction of differentiation, in protocols for the isolation of cardiac cells and in the tracking of cardiac cells after transplantation in vivo; we will also describe lentivirally-mediated gene delivery uses, such as the induction of a phenotype of interest in a target cell or the treatment of cardiovascular diseases. In addition, a section of the review will be dedicated to reprogramming approaches, focusing attention on the generation of pluripotent stem cells and on transdifferentiation, two emerging strategies for the production of cardiac myocytes from human cells and for the investigation of human diseases. Finally, in order to give a perspective on their future clinical use we will critically discuss advantages and disadvantages of lentivirus-based strategies for the treatment of cardiovascular diseases.

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Direct conversion of human fibroblasts to multilineage blood progenitors

Cited by 653 publications

References 46 publications

A short history of hemogenic endothelium

A short history of hemogenic endothelium

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function

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