Abstract:
:Small molecules (SM) can greatly enhance the efficiency of induced pluripotent stem (iPS) cell generation, but the mechanisms by which they act have not been fully explored. We show here that an SM cocktail (NaB, PD03259, and SB431542) significantly promotes iPS cell generation from human fibroblasts, and NaB is more potent than the other two common histone deacetylase inhibitors (valproic acid and Trichostatin A) in promoting cellular reprogramming. Our data indicate that the SM cocktail substantially upregulates the miR302/367 cluster expression by increasing the stability and transcriptional level of this microRNA (miRNA) cluster in a manner dependent on the four defined transcription factors (TFs). Among the four TFs, Oct4 in particular appears to be required for the induction of the miR302/367 cluster by the SM cocktail. We also found that NaB alone can enhance the TFs-dependent upregulation of the miR302/367 cluster. Using a promoter reporter assay, we show that the SM cocktail remarkably enhanced the transcriptional activity of the four TFs in the miR302/367 promoter. Notably, attenuation of miRNA302/367 using a miRZip impairs the ability of the SM cocktail in promoting reprogramming. Collectively, these findings suggest that the SM cocktail promotes reprogramming at least partly through the induction of the miR302/367 cluster expression. Further insights into this process may pave the way for the generation of iPS cells using only SM cocktails.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Zhang Z,Wu WSdoi
10.1089/scd.2012.0650subject
Has Abstractpub_date
2013-08-15 00:00:00pages
2268-77issue
16eissn
1547-3287issn
1557-8534journal_volume
22pub_type
杂志文章abstract::Most disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (Abeta) peptides as a hallmark of AD pathogenesis. Here we report the in vitro basis for a potential autologous stem cell-based strategy for widespread delivery of enzymatic activities ag...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0045
更新日期:2010-05-01 00:00:00
abstract::The optimization of defined growth conditions is necessary for the development of clinical application of human embryonic stem cells (hESCs). Current research has focused on developing defined media formulations for long-term culture of hESCs with little attention on the establishment of defined substrates for hESC pr...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0410
更新日期:2009-10-01 00:00:00
abstract::Recent studies have focused on transcriptional regulation and gene expression profiling of human embryonic stem cells (hESCs). However, little information is available regarding the relationship between RNA expression and transcriptional regulation, which is critical in the complete understanding of pluripotency and d...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.15.315
更新日期:2006-06-01 00:00:00
abstract::There is an increasing need for an animal model that can be used to translate basic research into clinical therapy. We documented the differentiation and functional competence of embryonic stem cell (ESC)-derived endothelial cells in baboons. Baboon angioblasts were sequentially differentiated from embryoid body cultu...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0313
更新日期:2013-02-15 00:00:00
abstract::Induced pluripotent stem cell (iPSC) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10-30 days). Conventional iPSC reprogramming was achieved using lentiviral or simple retroviral vectors. Retroviral reprogramming has flaws of insertional mutagenesis, uncont...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2013.0621
更新日期:2014-06-15 00:00:00
abstract::Small-molecule inhibitors of glycogen synthase kinase 3β (GSK3β) have demonstrated strong anti-leukemia effects in preclinical studies. Here, we investigated the effect of GSK3β inhibitor 6-Bromoindirubin-3-oxime (BIO) previously shown to inhibit leukemia cell growth in vitro and of animal models on hematopoietic rege...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0230
更新日期:2015-03-15 00:00:00
abstract::Novel cell-based and gene therapies represent promising approaches for the treatment of incurable diseases, including cancer. Following the success of the hematopoietic stem cell-based transplantation, other populations of adult progenitor cells, including mesenchymal stem cells (MSCs), have been identified as powerfu...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2010.0223
更新日期:2011-01-01 00:00:00
abstract::Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitocho...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0072
更新日期:2016-07-15 00:00:00
abstract::Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic OPLL. To date, the specific molecular pathogenesis of OPLL has not been clearly elucidated. In this study, bone marrow-derived mesenchymal stem cells obtained from healthy donors (HD-MSCs) and patients with OPLL (OPLL-MSCs) were cul...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0117
更新日期:2020-12-01 00:00:00
abstract::Nonpluripotent neural progenitor cells (NPCs) derived from the human fetal central nervous system were found to express a number of messenger RNA (mRNA) species associated with pluripotency, such as NANOG, REX1, and OCT4. The expression was restricted to small subpopulations of NPCs. In contrast to pluripotent stem ce...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0346
更新日期:2017-06-15 00:00:00
abstract::Spiral ganglion neurons (SGNs) are usually damaged in sensorineural hearing loss. SGN-derived neural stem cells (NSCs) have been identified and proposed to differentiate into neurons to replace damaged SGNs. However, it remains obscure whether SGN-NSC-derived neurons (ScNs) are electrophysiologically functional and po...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0345
更新日期:2016-05-15 00:00:00
abstract::Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differen...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0409
更新日期:2016-01-01 00:00:00
abstract::Recent studies have revealed that mesenchymal stem cells (MSCs) have a great potential in therapeutic applications. The low efficiency of MSC recruitment and homing to sites of diseased organ tissue, however, remains a major hurdle in their application for treatment of diseases. Stress is commonly associated with vari...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0243
更新日期:2015-03-01 00:00:00
abstract::The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that i...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0089
更新日期:2017-09-15 00:00:00
abstract::We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0520
更新日期:2010-09-01 00:00:00
abstract::The development of the heart is essential for embryogenesis and precedes development of other organs. However, the mechanisms involved in embryonic cardiac development are ill-defined. Recent evidence suggests that Smad and Wnt signaling pathways are important in stem cell fate determination and their commitment to ca...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.15.29
更新日期:2006-02-01 00:00:00
abstract::The field of regenerative medicine has increasingly recognized the importance to be inspired by developmental processes to identify signaling pathways crucial for 3D organogenesis and tissue regeneration. Here, we aimed at recapitulating the first events occurring during limb development (ie, cell condensation and exp...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0216
更新日期:2013-11-01 00:00:00
abstract::The CD34 surface antigen has been recognized as a marker of hematopoietic stem cells (HSCs) and is widely used for HSC selection as well as for quality control in HSC transplantation. CD34 has been implicated in cytoadhesion signaling, and its expression has been suggested to reflect the activation state of hematopoie...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.0056
更新日期:2007-04-01 00:00:00
abstract::In the mammalian olfactory epithelium (OE), olfactory receptor neurons (ORNs) are continuously regenerated throughout the animal's lifetime. Horizontal basal cells (HBCs) in the OE express the epithelial marker keratin 5 (K5) and the stem cell marker Pax6 and are considered relatively quiescent tissue stem cells in th...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0011
更新日期:2015-08-15 00:00:00
abstract::In this work, we evaluated the expansion of human hematopoietic stem cells from umbilical cord blood in roller bottles. The Iscove's modified Dulbecco's medium, the Stem Pro 34-SFM medium, and the L-15 Leibovitz's medium for cultures in CO(2)-free atmosphere were assessed. At day 5 of culture, total colony forming uni...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0236
更新日期:2011-04-01 00:00:00
abstract::The difficulty in long-term expansion of mesenchymal stem cells (MSCs) using standard culture systems without the loss of their stem cell properties suggests that a critical feature of their microenvironment necessary for retention of stem cell properties is absent in these culture systems. We report here the reconsti...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0217
更新日期:2010-07-01 00:00:00
abstract::Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic β-cells and to improve glucose metabolism in experimental diabetic rodent models. Mesenchymal stem cells (MSCs) have been already proved to be multipotent. Recent work has attributed...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0490
更新日期:2011-02-01 00:00:00
abstract::In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a stan...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0588
更新日期:2014-07-15 00:00:00
abstract::Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0279
更新日期:2013-02-01 00:00:00
abstract::Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to unde...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0334
更新日期:2017-06-01 00:00:00
abstract::Multipotent bone marrow-derived mesenchymal stem/stromal cells (BMSCs) exhibit a finite life span after ex vivo expansion leading to cellular senescence. Many factors can contribute to this. Recently, our group has identified for the first time expression of the chemokine-like factor superfamily 8 (CMTM8) gene in cult...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0007
更新日期:2020-07-01 00:00:00
abstract::We describe a method of generating an enriched population of NCAM-positive cells from a human teratocarcinoma cell line (NTera2/D1) and their differentiation into midbrain dopaminergic neurons in the absence of the caudalizing factor retinoic acid (RA). NTera2 cells were induced to form embryoid bodies and then to gen...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.15.575
更新日期:2006-08-01 00:00:00
abstract::Embryonic stem (ES) cells are recognized as an excellent cell culture model for studying developmental mechanisms and their therapeutic modulations. The aim of this work was to define whether using magnetofection was an efficient way to manipulate stem cells genetically without adversely affecting their proliferation ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0064
更新日期:2008-02-01 00:00:00
abstract::Extraembryonic endoderm (XEN) cells are stem cell lines derived from primitive endoderm cells of inner cell mass in blastocysts. These cells have self-renewal properties and differentiate into visceral endoderm (VE) and parietal endoderm (PE) of the yolk sac. Recently, it has been reported that XEN cells can contribut...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0026
更新日期:2017-08-01 00:00:00
abstract::In a previous study we established colony assays suitable for studying murine adult (2-4 months) pancreatic progenitor cells plated in semisolid media containing methylcellulose and extracellular matrix proteins. Using these assays, we found robust in vitro progenitor cell activities (multilineage differentiation and ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0466
更新日期:2014-04-15 00:00:00