Abstract：
:Here we utilized the chromatin in vivo assay (CiA) mouse platform to directly examine the epigenetic barriers impeding the activation of the CiA:Oct4 allele in mouse embryonic fibroblasts (MEF)s when stimulated with a transcription factor. The CiA:Oct4 allele contains an engineered EGFP reporter replacing one copy of the Oct4 gene, with an upstream Gal4 array in the promoter that allows recruitment of chromatin modifying machinery. We stimulated gene activation of the CiA:Oct4 allele by binding a transcriptional activator to the Gal4 array. As with cellular reprograming, this process is inefficient with only a small percentage of the cells re-activating CiA:Oct4 after weeks. Epigenetic barriers to gene activation potentially come from heavy DNA methylation, histone deacetylation, chromatin compaction, and other posttranslational marks (PTM) at the differentiated CiA:Oct4 allele in MEFs. Using this platform, we performed a high-throughput chemical screen for compounds that increased the efficiency of activation. We found that Azacytidine and newer generation histone deacetylase (HDAC) inhibitors were the most efficient at facilitating directed transcriptional activation of this allele. We found one hit form our screen, Mocetinostat, improved iPSC generation under transcription factor reprogramming conditions. These results separate individual allele activation from whole cell reprograming and give new insights that will advance tissue engineering.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Headley KM,Kedziora KM,Alejo A,Lai EZ,Purvis JE,Hathaway NAdoi
10.1016/j.scr.2019.101470subject
Has Abstractpub_date
2019-07-01 00:00:00pages
101470eissn
1873-5061issn
1876-7753pii
S1873-5061(19)30100-Xjournal_volume
38pub_type
杂志文章abstract：:Osteogenesis Imperfecta (OI) is a rare autosomal dominant metabolic disorder caused by heterozygous mutations in the COL1A1 or COL1A2 genes, which encode the pro-α1(I) and pro-α2(I) chains of type I procollagen, respectively. A human induced pluripotent stem cell (iPSC) line, termed as CHFUi001-A, was generated from p...
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：:We studied the susceptibility of human embryonic stem cells and derived contractile embryoid bodies from WAO9, HUES-5 and HUES-16 cell lines to Coxsackievirus B infection. After validating stem cell-like properties and cardiac phenotype, Coxsackievirus B receptors CAR and DAF, as well as type I interferon receptors we...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2010.09.002
更新日期：2011-01-01 00:00:00
abstract：:Thrombocytopenia 2 (THC2) is a major type of inherited thrombocytopenia caused by the persistent ANKRD26 expression during the late stage of megakaryocytopoiesis. For the first time, we generated a human induced pluripotent stem cell (hiPSC) line SHAMUi001-A from the bone marrow hematopoietic progenitor cells of a THC...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.102002
更新日期：2020-10-01 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：:OCT4 and NANOG are core transcription factor genes in self-renewal, differentiation, and reprogramming. Here, we generated an OCT4-EGFP, NANOG-tdTomato dual reporter hiPSC line, KKUi001-A, on the basis of human induced pluripotent stem cells using CRISPR/Cas9 technology. EGFP and tdTomato reporter were inserted into b...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.101943
更新日期：2020-10-01 00:00:00
abstract：:We generated PSMi001-A and PSMi008-A hiPSC lines from two individuals belonging to a South African (SA) founder population in which the malignant KCNQ1-A341V mutation cosegregates with the Long QT Syndrome (LQTS) phenotype. PSMi001-A was derived from an asymptomatic KCNQ1-A341V mutation carrier, whereas PSMi008-A was ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101510
更新日期：2019-08-01 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
abstract：:A skin biopsy was obtained from a 14-year-old female patient with a history of Myelomeningocele. Dermal fibroblasts were isolated and reprogrammed with Sendai virus (SeV) vectors encoding OCT3/4, SOX2, KLF4, and c-MYC. The generated induced Pluripotent Stem Cell (iPSC) clones NTDi4_09A were free of genomically integra...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.05.007
更新日期：2018-08-01 00:00:00
abstract：:CHCHD2 mutation has been reported as a potential cause of a rare form of familial Parkinson's disease. Recently, a novel CHCHD2 mutation was identified in a family with Parkinson's disease. The dermal fibroblasts of the patient were obtained and successfully transformed into induced pluripotent stem cells(iPSCs), empl...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.08.011
更新日期：2018-10-01 00:00:00
abstract：:Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes mellitus presenting at childhood or adolescence, which eventually leads to pancreatic β-cells dysfunction. The underlying genetic basis of MODY disorders is haploinsufficiency, where loss-of-function mutations in a single allele cause the dia...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.06.013
更新日期：2018-08-01 00:00:00
abstract：:Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.04.015
更新日期：2016-05-01 00:00:00
abstract：:Leucine rich repeat kinase (LRRK2) is the most prevalent genetic cause for Parkinson's disease. LRRK2 p.G2385R is an Asian specific genetic risk factor for sporadic Parkinson's disease. We generated two induced pluripotent stem cells (iPSCs), IBMS-iPSC-018-09 and IBMS-iPSC-020-01, from the peripheral blood mononuclear...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.01.034
更新日期：2018-04-01 00:00:00
abstract：:The KCL018 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the DMPK gene encoding the dystrophia myotonica protein kinase (2200 trinucleotide repeats; 14 for the normal allele). The ICM was isolated using laser microsurg...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.01.004
更新日期：2016-03-01 00:00:00
abstract：:The outcomes of clinical trials using bone marrow stromal cell (BMSC) are variable; the degree of the expansion of BMSCs during clinical manufacturing may contribute to this variability since cell expansion is limited by senescence. Human BMSCs from aspirates of healthy subjects were subcultured serially until cell gr...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2013.07.005
更新日期：2013-11-01 00:00:00
abstract：:To develop cell therapies for damaged nervous tissue with human neural stem/progenitor cells (hNPCs), the risk of an immune response and graft rejection must be considered. There are conflicting results and lack of knowledge concerning the immunocompetence of hNPCs of different origin. Here, we studied the immunogenic...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2013.01.001
更新日期：2013-05-01 00:00:00
abstract：:Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small intestine (SI) Paneth cells (PCs) play a central role in orchestrating crypt architecture and their relationship with Lgr5+ve stem cells. Nevertheless, we previously showed that germline CSF-1 ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2012.12.001
更新日期：2013-03-01 00:00:00
abstract：:Salisphere-derived adult epithelial cells have been used to improve saliva production of irradiated mouse salivary glands. Importantly, optimization of the cellular composition of salispheres could improve their regenerative capabilities. The Rho Kinase (ROCK) inhibitor, Y27632, has been used to increase the prolifera...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101608
更新日期：2019-12-01 00:00:00
abstract：:Human teratoma is a germ cell tumor that contains normal tissues (e.g., hair, skin or cartilage) differentiated from embryonal germ layers. Because of the feature of this tumor, we hypothesized that human teratomas contain multipotent stem cells that can develop into various non-cancerous normal tissues. In this study...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101633
更新日期：2019-12-01 00:00:00
abstract：:Oligodendrocyte precursor cells (OPCs) differentiation from multipotent neural stem cells (NSCs) into mature oligodendrocytes is driven by thyroid hormone and mediated by thyroid hormone receptors (TRs). We show that several nuclear receptors display strong changes in expression levels between fetal and adult NSCs, wi...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101443
更新日期：2019-05-01 00:00:00
abstract：:Rabbit Embryonic Fibroblast (RbEF) cells (from Hycole hybrid rabbit foetus) were reprogrammed by lentiviral delivery of a self-silencing hOKSM polycistronic vector. The pluripotency of the newly generated RbiPSC was verified by the expression of pluripotency-associated markers and by in vitro spontaneous differentiati...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2017.03.010
更新日期：2017-05-01 00:00:00
abstract：:Heredity is the major factor contributing to the susceptibility to ankylosing spondylitis(AS). Janus kinase 2 (JAK2) has been associated with AS. Urine-derived cells from an AS patient with JAK2 mutation were used to generate induced pluripotent stem cells (iPSCs) with five episomal iPSC reprogramming vectors (pCXLE-h...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.101788
更新日期：2020-05-01 00:00:00
abstract：:To develop a disease model for the human 'brittle bone' disease, osteogenesis imperfecta, we have used gene editing to produce a facsimile of the patient heterozygous COL1A1 mutation in an established control iPSC line. The gene-edited line had a normal karyotype, expressed pluripotency markers and differentiated into...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101449
更新日期：2019-05-01 00:00:00
abstract：:Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.05.004
更新日期：2018-07-01 00:00:00
abstract：:Progenitor cells in the adult pancreas are potential sources of endocrine beta cells for treating type 1 diabetes. Previously, we identified tri-potent progenitor cells in the adult (2-4month-old) murine pancreas that were capable of self-renewal and differentiation into duct, acinar, and endocrine cells in vitro. The...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.11.015
更新日期：2016-01-01 00:00:00
abstract：:Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a five months-old boy with glycogen storage disease type II(GSD II, also known as Pompe disease, PD) carries compound mutations R608X E888X in GAA gene. PBMCs were reprogrammed us...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101621
更新日期：2019-12-01 00:00:00
abstract：BACKGROUND:Non-random segregation of DNA strands during stem cell replication has been proposed as a mechanism to minimize accumulated genetic errors in stem cells of rapidly dividing tissues. According to this hypothesis, an "immortal" DNA strand is passed to the stem cell daughter and not the more differentiated cell...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2015.01.005
更新日期：2015-03-01 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：:Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determi...
journal_title：Stem cell research
pub_type： 杂志文章,评审
doi：10.1016/j.scr.2017.09.005
更新日期：2017-10-01 00:00:00
abstract：:A recessive mutation in PLA2G6, which is known to cause a heterogeneous neurodegenerative clinical spectrum, has recently been shown to be responsible for autosomal-recessive familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cell...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2019.101432
更新日期：2019-05-01 00:00:00
abstract：:Spinocerebellar ataxia type-12 (SCA12) is a neurological disorder caused due to triplet (CAG) repeat expansion in 5' UTR of PPP2R2B. It is one of the most prominent SCA-subtype in Indian population and till date no patient specific models have been described. Human-induced-pluripotent-stem cell (HiPSC) based disease m...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.08.008
更新日期：2018-08-01 00:00:00
