Abstract:
:The Mesenchymal-to-Epithelial Transition (MET) has been recognized as a crucial step for successful reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs). Thus, it has been demonstrated, that the efficiency of reprogramming can be enhanced by promoting an epithelial expression program in cells, with a concomitant repression of key mesenchymal genes. However, a detailed characterization of the epithelial transition associated with the acquisition of a pluripotent phenotype is still lacking to this date. Here, we integrate a panel of morphological approaches with gene expression analyses to visualize the dynamics of episomal reprogramming of human fibroblasts to iPSCs. We provide the first ultrastructural analysis of human fibroblasts at various stages of episomal iPSC reprogramming, as well as the first real-time live cell visualization of a MET occurring during reprogramming. The results indicate that the MET manifests itself approximately 6-12days after electroporation, in synchrony with the upregulation of early pluripotency markers, and resembles a reversal of the Epithelial-to-Mesenchymal Transition (EMT) which takes place during mammalian gastrulation.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Høffding MK,Hyttel Pdoi
10.1016/j.scr.2014.11.003subject
Has Abstractpub_date
2015-01-01 00:00:00pages
39-53issue
1eissn
1873-5061issn
1876-7753pii
S1873-5061(14)00139-1journal_volume
14pub_type
杂志文章abstract::Best's disease (BD) is an inherited retinal degenerative disease caused by mutations in BEST1 gene. A human induced pluripotent stem cell (iPSC) line has been generated with integration-free Sendai virus method from peripheral blood mononuclear cells (PBMCs) of a BD patient carrying c.888C > A mutation in BEST1 gene. ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101459
更新日期:2019-07-01 00:00:00
abstract::Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into hepatic cells, including expandable hepato-blasts (HBs) and hepatocyte-like cells (HLCs) in vitro. Therefore, hESC-derived HBs have the potential to become a renewable cell source for cell therapy of serious liver damage. Howe...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2020.102010
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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 embryonic stem cell (hESC) line chHES-478 was derived from abnormal blastocyst diagnosed with albinism after preimplantation genetic diagnosis (PGD) treatment. DNA sequencing analysis confirmed that chHES-478 cell line carried a compound heterozygous mutation, c.896G>A(p.Arg299His) and c.929_930insC(p.Pro310Glnf...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.11.004
更新日期:2016-11-01 00:00:00
abstract::Pathological myopia (PM) is a retinal degenerative disease with an increasing prevalence in Asia. The peripheral blood mononuclear cells (PBMCs) from a patient with PM were successfully reprogrammed to induced pluripotent stem cells (iPSCs) using integration-free method, Sendai viral (SeV) vectors expressing OCT4, SOX...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.101369
更新日期:2019-01-01 00:00:00
abstract::X-linked Alport syndrome (XLAS) is a rare form of hereditary nephritis caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain. A skin biopsy was performed on one female patient with XLAS who carried a heterozygous p.G409S (c. 1225 G > A) mutation in the COL4A5 gene. A human-induced pluripotent s...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2020.101833
更新日期:2020-05-01 00:00:00
abstract::Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.01.017
更新日期:2016-03-01 00:00:00
abstract::Ectopic expression of HoxB4 in embryonic stem (ES) cells leads to an efficient production of hematopoietic cells, including hematopoietic stem/progenitor cells. Previous studies have utilized a constitutive HoxB4 expression system or tetracycline-regulated HoxB4 expression system to induce hematopoietic cells from ES ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2011.09.001
更新日期:2012-03-01 00:00:00
abstract::Extracellular signal-regulated kinases (ERKs) have many important functions during embryogenesis. However, their role in embryonic stem (ES) cells is controversial. Previous studies reported that, in contrast to mouse ES cells, human ES cells differentiate if ERK1/2 is inhibited. We reexamined the role of ERK1/2 in hu...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2010.06.002
更新日期:2010-09-01 00:00:00
abstract::An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of com...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.01.007
更新日期:2018-03-01 00:00:00
abstract::An important practical limitation of the three-dimensional geometry of stem-cell derived intestinal organoids is that it prevents easy access to the apical epithelium for testing food components, microorganisms, bioactive and toxic compounds. To this end, we here report on a new robust method for generating confluent ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.02.013
更新日期:2018-04-01 00:00:00
abstract::SOX4 has been shown to promote neuronal differentiation both in the adult and embryonic neural progenitors. Ectopic SOX4 expression has also been shown to inhibit oligodendrocyte differentiation in mice, however the underlying molecular mechanisms remain poorly understood. Here we demonstrate that SOX4 regulates trans...
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
abstract::Androgen-deprivation is a mainstay of therapy for advanced prostate cancer but tumor regression is usually incomplete and temporary because of androgen-independent cells in the tumor. It has been speculated that these tumor cells resemble the stem/progenitor cells of the normal prostate. The purpose of this study was ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.04.005
更新日期:2014-07-01 00:00:00
abstract::Asparagine synthetase (ASNS) deficiency (ASNSD; MIM #615574) is a rare neurodevelopmental disorder caused by mutations in the ASNS gene. The ASNS gene maps to cytogenetic band 7q21.3 and is 35 kb long. ASNSD is characterised by congenital microcephaly, severely delayed psychomotor development, seizures, and hyperekple...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101583
更新日期:2019-12-01 00:00:00
abstract::The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs). MB49 bladder cancer stem cells (MCSCs) were isolated by a combination of the limited dilution method and t...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.04.006
更新日期:2014-07-01 00:00:00
abstract::Human FOXH1 (Forkhead Box H1) gene encodes a human homolog of Xenopus forkhead activing signal transducer-1 and has been shown to play an important role in mesendoderm formation in X. tropicalis and mice. However, little is known about the function of FOXH1 in human development. Here we generated a FOXH1 homozygous kn...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2020.102121
更新日期:2020-12-10 00:00:00
abstract::Optimization of pluripotent stem cell expansion and differentiation is facilitated by biological tools that permit non-invasive and dynamic monitoring of pluripotency, and the ability to select for an undifferentiated input cell population. Here we report on the generation and characterisation of clonal human embryoni...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.05.006
更新日期:2014-09-01 00:00:00
abstract::Tumor protein p63 (p63) encodes for a transcription factor of the p53 family and is a marker for respiratory basal cells. Based on a NKX2.1 knock-in reporter cell line from human induced pluripotent stem cells (hiPSCs) (MHHi06-A-2) we established a NKX2.1/p63 double transgenic knock-in reporter cell line using TALEN t...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101659
更新日期:2020-01-01 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::Fanconi anemia is a genetic bone marrow failure syndrome. The current treatment options are suboptimal and do not prevent the eventual onset of aplastic anemia requiring bone marrow transplantation. We previously showed that resveratrol, an antioxidant and an activator of the protein deacetylase Sirt1, enhanced hemato...
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
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journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.01.029
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
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::Human circulating endothelial progenitor cells isolated from peripheral blood generate in culture cells with features of endothelial cells named late-outgrowth endothelial colony-forming cells (ECFC). In adult blood, ECFC display a constant quantitative and qualitative decline during life span. Even after expansion, i...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.03.001
更新日期:2014-05-01 00:00:00
abstract::The human iPSC cell line, CARS-FiPS4F1 (ESi064-A), derived from dermal fibroblast from the apparently healthy carrier of the mutation of the gene SACSIN, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors. The pluripotency was assessed by immunocytochemist...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.10.016
更新日期:2018-12-01 00:00:00
abstract::Many studies have compared the genetic and epigenetic profiles of human induced pluripotent stem cells (hiPSCs) to human embryonic stem cells (hESCs) and yet the picture remains unclear. To address this, we derived a population of neural precursor cells (NPCs) from the H1 (WA01) hESC line and generated isogenic iPSC l...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2013.11.010
更新日期:2014-03-01 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::Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (i...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.09.024
更新日期:2016-11-01 00:00:00
abstract::Among the known causative genes of familial ALS, SOD1mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not c...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2020.101924
更新日期:2020-07-25 00:00:00
abstract::FOS is component of the AP-1 complex and has been reported to be involved in many cellular functions, including cell proliferation, differentiation, survival, angiogenesis, hematopoiesis and cancer progress. To further understand the exact role of FOS in these processes, here we created two FOS knockout human embryoni...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101479
更新日期:2019-08-01 00:00:00