Abstract:
:Aside from its role in cell membrane integrity, cholesterol is a key component in steroid hormone production. The vital functions of steroid hormones such as estrogen, testosterone, glucocorticoids (Gcrts) and mineralocorticoids (Mnrts) in perinatal and adult life are well understood; however, their role during early embryonic development remains largely unexplored. Here we show that siRNA-mediated perturbation of steroid hormone production during mesoderm formation has important consequences on cardiac differentiation in mouse embryonic stem cells (mESC). Both Gcrts and Mnrts are capable of driving cardiac differentiation in mESC. Interestingly, the Gcrt receptor is widely expressed during gastrulation in the mouse, and is exclusively localized in the nuclei-and thus active-in visceral endoderm cells, suggesting that it functions much earlier than previously anticipated. We therefore studied Gcrt signaling in mESC as a model of the gastrulating embryo, and found that Gcrt signaling regulates expression of the transcription factor Hnf4a and the secreted Nodal and BMP inhibitor Cer1 in the early visceral endoderm. RNAi-mediated knockdown of Gcrt function blocked cardiomyocyte differentiation, with limited effects on other cardiovascular cell types including vascular endothelial cells and smooth muscle. Furthermore, the cardiogenic effect of Gcrts required Hnf4a and paracrine Cer1. These results establish a novel function for cholesterol-derived steroid hormones and identify Gcrt signaling in visceral endoderm cells as a regulator of Cer1 and cardiac fate.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Cabral-Teixeira J,Martinez-Fernandez A,Cai W,Terzic A,Mercola M,Willems Edoi
10.1016/j.scr.2015.04.010subject
Has Abstractpub_date
2015-07-01 00:00:00pages
88-95issue
1eissn
1873-5061issn
1876-7753pii
S1873-5061(15)00061-6journal_volume
15pub_type
杂志文章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::Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of the liver metabolism due to functional deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in overproduction of oxalate which complexes with calcium to form insoluble calcium-oxalate salts in...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101467
更新日期:2019-07-01 00:00:00
abstract::Human skin fibroblasts were isolated from a 40-year-old hereditary spastic paraplegia patient carrying an intronic splice site mutation (c.1687+2T>A) in SPAST, leading to hereditary spastic paraplegia type 4 (SPG4). Fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.09.022
更新日期:2016-11-01 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::Recent clinical trials show the efficacy of Adipose-derived Stromal Cells (ASCs) in contrasting the osteoarthritis scenario. Since it is quite accepted that ASCs act predominantly through a paracrine mechanism, their secretome may represent a valid therapeutic substitute. The aim of this study was to investigate the e...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101463
更新日期:2019-07-01 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::Both BMP and Wnt signaling control stem cells in bulge/dermal papilla, intestinal crypt, and bone marrow. To explore their roles in the limbal niche, which govern corneal epithelial homeostasis, we established an in vitro model of sphere growth by reunion between single limbal epithelial progenitor cells (LEPCs) and a...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.01.003
更新日期:2014-03-01 00:00:00
abstract::The future application of human embryonic stem cells (hESC) for therapeutic approaches requires the development of xeno-free culture conditions to prevent the potential transmission of animal pathogens or xenobiotic substances to hESC. An important component of the majority of hESC culture systems developed is the req...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2010.08.002
更新日期:2011-01-01 00:00:00
abstract::Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs) from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28, SOX2, KLF4, OCT4 an...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.02.040
更新日期:2016-05-01 00:00:00
abstract::We established three iPSC lines from postmortem-cultured fibroblasts derived following the sudden unexpected death of an 8-year-old girl with Lennox-Gastaut syndrome, who turned out to have the R551H-mutant STXBP1 gene. These iPSC clones showed pluripotent characteristics while retaining the genotype and demonstrated ...
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::It has been very difficult, if not impossible, to establish mouse induced pluripotent stem cells (iPSCs) from differentiated cells, such as fibroblasts, without leukemia inhibitory factor (LIF). We have established and maintained LIF-independent iPSCs for longer than 120 days with modified Oct4 along with Sox2, Klf4, ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2015.08.005
更新日期:2015-09-01 00:00:00
abstract::We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 51years old female patient homozygous for the mutation c.535 G>A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1), not associated with deafness. The hiPSCs, generated using f...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2018.04.003
更新日期:2018-05-01 00:00:00
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...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2019.101529
更新日期:2019-10-01 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 Genea079 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype w...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2016.02.015
更新日期:2016-03-01 00:00:00
abstract::Satellite cells (SCs) are the resident stem cells of skeletal muscle tissue which play a major role in muscle adaptation, e.g. as a response to physical training. The aim of this study was to examine the effects of an intermittent lactate (La) treatment on the proliferation and differentiation of C2C12 myoblasts, simu...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2014.03.004
更新日期:2014-05-01 00:00:00
abstract::Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs). However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration ma...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2015.05.001
更新日期:2015-07-01 00:00:00
abstract::Constant neuroregeneration in adult olfactory epithelium maintains olfactory function by basal stem cell proliferation and differentiation to replace lost olfactory sensory neurons (OSNs). Understanding the mechanisms regulating this process could reveal potential therapeutic targets for stimulating adult olfactory ne...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2020.102061
更新日期:2020-12-01 00:00:00
abstract::The aim of this study was to determine whether the growth and differentiation of limbal epithelial stem cell cultures could be controlled through manipulation of the oxygen tension. Limbal epithelial cells were isolated from corneoscleral disks, and cultured using either feeder cells in a growth medium supplemented wi...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2013.01.004
更新日期:2013-05-01 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::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::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::Induced-pluripotent stem cells (iPSCs) are a potential alternative cell source in regenerative medicine, which includes the use of differentiated iPSCs for cell therapies to treat coronary artery and/or peripheral arterial diseases. Late-outgrowth endothelial progenitor cells (late-EPCs) are a unique primary cell pres...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2012.11.006
更新日期:2013-03-01 00:00:00
abstract::Human embryonic stem (hES) cells have the dual ability to self-renew and differentiate into specialized cell types. However, in order to realize the full potential of these cells it is important to understand how the genes responsible for their unique characteristics are regulated. In this study we examine the regulat...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2011.10.003
更新日期:2012-03-01 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::Insulin-like growth factor 1 (IGF-1) plays an important role in the regulation of tooth root development, and stem cells from apical papilla (SCAPs) are responsible for the formation of root pulp and dentin. To date, it remains unclear whether IGF-1 can regulate the function of SCAPs. In this study, SCAPs were isolate...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2011.12.005
更新日期:2012-05-01 00:00:00
abstract::Human iPSC line N44SV.5 was generated from primary normal human dermal fibroblasts belonging to the European mitochondrial haplogroup U. For this purpose, reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus. ...
journal_title:Stem cell research
pub_type: 杂志文章
doi:10.1016/j.scr.2015.12.010
更新日期:2016-01-01 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::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::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