Abstract：
:Friedreich's ataxia is caused by large homozygous, intronic expansions of GAA repeats in the frataxin (FXN) gene, resulting in severe downregulation of its expression. Pathogenic repeats are located in intron one, hence patients express unaffected FXN protein, albeit in low quantities. Although FRDA symptoms typically afflict the nervous system, hypertrophic cardiomyopathy is the predominant cause of death. Our studies were conducted using cardiomyocytes differentiated from induced pluripotent stem cells derived from control individuals, FRDA patients, and isogenic cells corrected by zinc finger nucleases-mediated excision of pathogenic expanded GAA repeats. This correction of the FXN gene removed the primary trigger of the transcription defect, upregulated frataxin expression, reduced pathological lipid accumulation observed in patient cardiomyocytes, and reversed gene expression signatures of FRDA cardiomyocytes. Transcriptome analyses revealed hypertrophy-specific expression signatures unique to FRDA cardiomyocytes, and emphasized similarities between unaffected and ZFN-corrected FRDA cardiomyocytes. Thus, the iPSC-derived FRDA cardiomyocytes exhibit various molecular defects characteristic for cellular models of cardiomyopathy that can be corrected by genome editing of the expanded GAA repeats. These results underscore the utility of genome editing in generating isogenic cellular models of FRDA and the potential of this approach as a future therapy for this disease.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Li J,Rozwadowska N,Clark A,Fil D,Napierala JS,Napierala Mdoi
10.1016/j.scr.2019.101529subject
Has Abstractpub_date
2019-10-01 00:00:00pages
101529eissn
1873-5061issn
1876-7753pii
S1873-5061(19)30159-Xjournal_volume
40pub_type
杂志文章abstract：:Neuroblasts represent the predominant migrating cell type in the adult mouse brain. There are, however, increasing evidences of migration of other neural precursors. This work aims at identifying in vivo endogenous early neural precursors, different from neuroblasts, able to migrate in response to brain injuries. The ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2014.11.006
更新日期：2015-01-01 00:00:00
abstract：:The KCL034 human embryonic stem cell line was derived from a normal healthy blastocyst donated for research. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment and under ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.12.034
更新日期：2016-01-01 00:00:00
abstract：:Human epicardium-derived cells (EPDC) were reprogrammed to generate two iPSC lines, MCDU1i-EPDC and MCDU2i-EPDC, by nucleofection of episomal-based plasmids expressing the reprogramming factors OCT4, SOX2, KLF4, c-MYC, NANOG and LIN28. Pluripotency was confirmed in vitro by immunofluorescence analysis and embryoid bod...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2017.02.007
更新日期：2017-04-01 00:00:00
abstract：:Little is known about the functions of downstream regulatory element antagonist modulator (DREAM) in embryonic stem cells (ESCs). However, DREAM interacts with cAMP response element-binding protein (CREB) in a Ca(2+)-dependent manner, preventing CREB binding protein (CBP) recruitment. Furthermore, CREB and CBP are inv...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.03.001
更新日期：2016-05-01 00:00:00
abstract：:We report here the generation of human iPS cell line UKKi009-A from dermal fibroblasts of a patient carrying heterozygous mutation c.3035-3045delTCCCTCGATGC, p.Leu1012Pro (fs*55) in KCNH2 gene leading to long QT syndrome type 2 (LQT2). We used the Sleeping Beauty transposon-based plasmids expressing OSKM along with mi...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.12.039
更新日期：2016-03-01 00:00:00
abstract：:The conventional method of culturing human embryonic stem cells (hESC) is on two-dimensional (2D) surfaces, which is not amenable for scale up to therapeutic quantities in bioreactors. We have developed a facile and robust method for maintaining undifferentiated hESC in three-dimensional (3D) suspension cultures on ma...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2009.02.005
更新日期：2009-05-01 00:00:00
abstract：:Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NA...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.10.003
更新日期：2016-11-01 00:00:00
abstract：:A DAND5-control human iPSC line was generated from the urinary cells of a phenotypically normal donor. Exfoliated renal epithelial (RE) cells were collected and reprogrammed into iPSCs using Sendai virus reprogramming system. The pluripotency, in vitro differentiation potential, karyotype stability, and the transgene-...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.04.015
更新日期：2018-05-01 00:00:00
abstract：:Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG repeat expansion in the region of the ATXN3 gene. The main feature of SCA3 is progressive ataxia, which affects balance, gait, and speech. Urine cells (UCs) of a SCA3 patient were successfully translated to induced...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.01.027
更新日期：2018-04-01 00:00:00
abstract：:Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Amniotic fluid (AF) cells are easy to obtain from routinely scheduled procedures for prenatal diagnosis and iPS cells have been generated from human AF. H...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.09.009
更新日期：2015-11-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.101907
更新日期：2020-07-05 00:00:00
abstract：:Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of esta...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.05.003
更新日期：2016-07-01 00:00:00
abstract：:The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell-cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membra...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.09.010
更新日期：2015-11-01 00:00:00
abstract：:Angelman syndrome (AS) is a neurodevelopmental disorder with leading symptoms of happy demeanor, intellectual disability, ataxia and seizures. AS can be caused by genetic and epigenetic aberrations, resulting in the absence of functional UBE3A protein in the brain. UBE3A is an imprinted gene, which is, in neurons of t...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.09.015
更新日期：2018-12-01 00:00:00
abstract：:Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutations in either CREBBP (RSTS1) or EP300 (RSTS2) genes. We characterized 3 iPSC lines generated by Sendai from blood of RSTS1 patients with un...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101553
更新日期：2019-10-01 00:00:00
abstract：:Human iPSC line, iPSC-ADM01(SYSUi001-A), was generated from a 70-year-old male patient with sporadic Alzheimer's disease, using non-integrative reprogramming method. This cell line shows pluripotency both in vitro and in vivo, and has a normal karyotype. ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.101375
更新日期：2019-03-01 00:00:00
abstract：:Human embryonic stem cells (hESCs) offer new avenues for studying human development and disease progression in addition to their tremendous potential toward development of cell-replacement therapies for various cellular disorders. We have earlier reported the derivation and characterization of Relicell(®) hES1, the fi...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2010.07.001
更新日期：2010-11-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2014.11.002
更新日期：2015-01-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101485
更新日期：2019-08-01 00:00:00
abstract：:The long QT syndrome type 3 (LQT3) is currently the 3rd most prevalent of the 15 known types of LQT syndrome. Cardiac events in LQT3 are less frequent than LQT1 and LQT2, but more likely to be fatal. LQT3 is caused by mutation in gene SCN5A, which codes for the Nav1.5 Na+ channel. Herein, we have generated a human emb...
journal_title：Stem cell research
pub_type： 杂志文章
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更新日期：2021-01-25 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.10.005
更新日期：2018-12-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2017.09.001
更新日期：2017-10-01 00:00:00
abstract：:Myeloid ecotropic viral integration site 1 (MEIS1) plays an essential role in the development of several embryonic organs, such as the central nervous system and eyes. To further investigate the role of MEIS1 in embryonic development, herein, we generated a MEIS1 homozygous knockout human embryonic stem cell (hESC) li...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.102069
更新日期：2020-12-01 00:00:00
abstract：:Umbilical cord blood (UCB) transplantation has emerged as a promising therapy, but it is challenged by scarcity of stem cells. Eltrombopag is a non-peptide, thrombopoietin (TPO) receptor agonist, which selectively activates c-Mpl in humans and chimpanzees. We investigated eltrombopag's effects on human UCB hematopoiet...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2012.05.001
更新日期：2012-09-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101461
更新日期：2019-07-01 00:00:00
abstract：:Conditioned medium (CM) derived from engineered cells often facilitates the cost-effective culture of a variety of stem cells. Growing emphasis on the importance of rigor and reproducibility in lab-based science requires development of best practices approaches, including quality control procedures for the assessment ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101430
更新日期：2019-05-01 00:00:00
abstract：:Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's disease (AD) but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the util...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.04.008
更新日期：2015-07-01 00:00:00
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journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.05.007
更新日期：2015-07-01 00:00:00
abstract：:Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of m...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.04.007
更新日期：2016-05-01 00:00:00
abstract：:An 83-year old Alzheimer's disease (AD) male patient donated his Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system used to reprogram PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency marker...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.11.008
更新日期：2018-12-01 00:00:00
