A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models

Ding, Qiurong; Lee, Youn-Kyoung; Schaefer, Esperance A.; Peters, Derek T; Veres, Adrian; Kim, Kevin J.; Kuperwasser, Nicolas; Motola, Daniel L.; Meißner, Torsten; Hendriks, William T.; Trevisan, Marta; Gupta, Rajat M.; Moisan, Annie; Banks, Eric; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Dahéron, Laurence; Zhang, Feng; Rubin, Lee L.; Peng, Leilei; Chung, Raymond T.; Musunuru, Kiran; Cowan, Chad A.

doi:10.1016/j.stem.2012.11.011

Cited by 466 publications

(379 citation statements)

References 46 publications

Supporting

Mentioning

370

Contrasting

Unclassified

Order By: Relevance

“…Differentiation of motor neurons (MNs) from human iPSCs was performed as previously described 30. Briefly, pluripotent stem cells were propagated on matrigel with StemBeads.…”

Section: Methodsmentioning

confidence: 99%

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Muhammad

Kim

Epifantseva

et al. 2018

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

ObjectiveTo investigate transplantation of rat Schwann cells or human iPSC‐derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage.MethodsPrimary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation. Human‐induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells, and subsequently toward a Schwann cell lineage via two different protocols. Cell types were characterized using flow cytometry, immunocytochemistry, and transcriptomics. Rat Schwann cells and human iPSC derivatives were transplanted into (1) nude rats pretreated with lysolecithin to induce demyelination or (2) a transgenic rat model of dysmyelination due to PMP22 overexpression.ResultsRat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration. Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal‐appearing myelin. Human iPSC‐derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin.InterpretationThese results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve. However, lack of reliable technology for generating human iPSC‐derived Schwann cells for transplantation therapy remains a barrier in the field.

show abstract

“…Differentiation of motor neurons (MNs) from human iPSCs was performed as previously described 30. Briefly, pluripotent stem cells were propagated on matrigel with StemBeads.…”

Section: Methodsmentioning

confidence: 99%

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Muhammad

Kim

Epifantseva

et al. 2018

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

show abstract

“…In side-by-side comparisons to ZFNs, TALENs exhibit comparable efficacy and lower toxicity (35). As demonstrated in a recent study, TALENs have greatly facilitated genome editing in hPSCs for generating disease models (36).…”

Section: Genome Editing With Synthetic Nucleasesmentioning

confidence: 98%

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

Suzuki

Kim

et al. 2014

Journal of Biological Chemistry

115

View full text Add to dashboard Cite

Human pluripotent stem cells (hPSCs) offer unprecedented opportunities to study cellular differentiation and model human diseases. The ability to precisely modify any genomic sequence holds the key to realizing the full potential of hPSCs. Thanks to the rapid development of novel genome editing technologies driven by the enormous interest in the hPSC field, genome editing in hPSCs has evolved from being a daunting task a few years ago to a routine procedure in most laboratories. Here, we provide an overview of the mainstream genome editing tools, including zinc finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeat/CAS9 RNA-guided nucleases, and helper-dependent adenoviral vectors. We discuss the features and limitations of these technologies, as well as how these factors influence the utility of these tools in basic research and therapies.The discovery of induced pluripotent stem cells (iPSCs) 5 seven years ago has reignited the enthusiasm for cell-based therapy. The ability of iPSCs to undergo unlimited division while maintaining genomic integrity provides a way to overcome the senescence barrier of aged somatic cells. The capacity of iPSCs to differentiate into cells of the three germ layers has been extensively documented in the field. Taken together, it is not hard to appreciate why human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine (Fig. 1). One area that has drawn great interest is correction of genetic diseases in patient-specific hiPSCs with a prospect of personalized cell therapy.Pluripotent stem cells are especially amenable for genome editing because they can undergo extensive tissue culture manipulations, such as drug selection and clonal expansion, while still maintaining their pluripotency and genome stability. Gene targeting in mouse embryonic stem cells by homologous recombination (HR) has proven to be a staple technique for studying gene function (1, 2). However, the same strategy does not translate well into human embryonic stem cells (hESCs) or hiPSCs (3). Although the classical HR method has been successfully used to generate knock-in reporter lines and to correct gene mutations in hESCs, the reported targeting efficiencies are at least several orders of magnitude lower than what is achievable in mouse embryonic stem cells (4,5). This is likely due to the intrinsic differences in the DNA repair process between humans and mice, as measures to improve single-cell survival and DNA transfection did not have a dramatic effect on gene targeting efficiency (6, 7). However, other methods aimed at promoting HR proved more fruitful (3). In the past several years, there has been a spike of interest in genome editing in hESCs and hiPSCs, possibly due to the potential of this technology in modeling and correcting a myriad of genetic diseases (8,9). This has fueled a rapid development in novel technologies for targeted modification of the human genome. Here, we aim to provide a timely u...

show abstract

“…Circulating LDL are cleared by the LDL receptor in the liver and other tissues 40 . Proposed functions for sortilin in reducing plasma cholesterol comprise its action as a hepatic clearance receptor for LDL 39,41 or a role in anterograde sorting of nascent lipoprotein particles from the TGN to lysosomes, effectively reducing the output of VLDL by the liver 38,42 . In contrast, a possible activity of sortilin in increasing plasma cholesterol involves its ability to facilitate secretion of VLDL from hepatocytes 14 .…”

Section: Sortilin a Risk Factor For Hypercholesterolemia And Myocardmentioning

confidence: 99%

Protein sorting gone wrong – VPS10P domain receptors in cardiovascular and metabolic diseases

Schmidt

Willnow

2016

Atherosclerosis

View full text Add to dashboard Cite

VPS10P domain receptors are a unique class of sorting receptors that direct intracellular transport of target proteins in neurons and that play central roles in neurodegenerative processes. Surprisingly, genome-wide association studies now implicate the very same receptors in cardiovascular and metabolic disturbances. In this review, we discuss current findings that uncovered some of the molecular mechanisms whereby sorting receptors, such as SORLA, sortilin, and SORCS1 control homeostasis in cardiovascular and metabolic tissues, and how they promote hypercholesterolemia, atherosclerosis, obesity, and diabetes, when being altered.3

show abstract

A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models

Cited by 466 publications

References 46 publications

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

A Cut above the Rest: Targeted Genome Editing Technologies in Human Pluripotent Stem Cells

Protein sorting gone wrong – VPS10P domain receptors in cardiovascular and metabolic diseases

Contact Info

Product

Resources

About