Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338281 | ENA |
REPOSITORIES: ENA
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Project description:Induced pluripotent stem cells (iPSC), which are generated from a patient’s own cells and used to produce transplantable tissues, may particularly benefit older patients who are more likely to suffer from degenerative diseases. However, iPSC generated from aged donors (A-iPSC) exhibit higher genomic instability, defects in apoptosis, and a blunted DNA damage response compared to iPSC generated from younger donors (Y-iPSC). This raises significant safety concerns, as transplantable tissues produced from A-iPSC may be functionally impaired and carry a higher risk of cancer development. When we consider the complex genomic and epigenetic variations that occur during aging, the genomic instability in A-iPSC is likely caused by multiple mechanims. Here, we introduce the first step toward unraveling this question with the discovery of a mechanism that contributes to A-iPSC instability. We demonstrated that A-iPSC exhibit excessive glutathione-mediated reactive oxygen species (ROS) scavenging activity, which blocks the DNA damage response and apoptosis and leads to genomic instability. We found that the pluripotency factor ZSCAN10 is poorly expressed in A-iPSC and addition of ZSCAN10 with the four Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC) used in iPSC reprogramming normalizes ROS/glutathione homeostasis and the DNA damage response and recovers A-iPSC genomic stability. Restoring the genomic stability of A-iPSC will ultimately enhance our ability to produce histocompatible functional tissues from patient’s own cells that are safe for transplantation.
2017-07-31 | GSE85365 | GEO
Project description:Zinc finger and SCAN domain containing 10 (Zscan10) was identified as a novel transcription factor in osteoclast differentiation by our previous study. However, the biological functions of Zscan10 have not been fully understood except its role in maintenance of genome stability and pluripotency in embryonic stem cells. Therefore, the purpose of this study is clarification of Zscan10 function in somatic cells, especially during osteoclast differentiation. First, Zscan10 KO RAW264 (KO) cells were established using CRISPR/Cas9 system and single cell sorting. Then, Control (Ctrl) and KO cells were differentiated into osteoclast by RANKL stimulation. As a result, TRAP activity and expression levels of differentiation marker genes, such as Nfatc1, were significantly increased and the expression of inhibitory factors, such as Irf8, was decreased in KO cells as compared to Ctrl cells. These results suggested that Zscan10 might regulate transcription of the genes which negatively control osteoclastogenesis. To understand the transcriptomes controlled by Zscan10, RNA-seq was performed and the stringent analyses identified significantly down-regulated Haptoglobin (Hp) in KO cells. Additionally, Zscan10 binding sequence was located near the genomic region of Hp gene locus. ChIP against Zscan10 followed by qPCR for the region revealed that Zscan10 binds to the region located near Hp gene locus and transcript start site, suggesting that Zscan10 may regulate transcription of Hp. Next, to examine the effect of Hp under Zscan10 mediated osteoclastogenesis, KO cells were treated with recombinant Hp (rHp). As a result, Hp treatment could suppress the elevated TRAP activity of KO cells without affecting cell viability. Furthermore, Hp KO mice exhibit decreased bone mass and increased osteoclast number, and Hp has been reported to be involved in suppression of osteoclastogenesis. Also, In hemolytic disease, Hp had been decreased and also bone density. These facts suggested that Zscan10 negatively regulates osteoclast differentiation through transcription of Hp.
2019-03-25 | GSE121320 | GEO
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
Project description:Human embryonic and induced pluripotent stem cells (hESCs and iPSCs) are being considered as sources of differentiated cells for drug development and cell therapy. Genomic stability of these cells is important for in vitro studies, and is critical for clinical applications. Of particular concern for cell therapy is the known association between genetic aberrations and tumorigenicity. Our results highlight the dynamic nature of genomic abnormalities in pluripotent stem cell culture and the need for frequent genomic monitoring of pluripotent stem cells destined for transplantation in order to determine the impact of specific genomic changes on phenotypic stability and clinical safety.
2011-02-15 | GSE25925 | GEO
Project description:Genome stability of chemically induced pluripotent stem cells with or without crotonic acid
| PRJNA1066557 | ENA
Project description:Analysis of genomic integrity of disease-corrected human induced pluripotent stem cells by exome sequencing
| EGAD00001000086 | EGA
Project description:Analysis of genomic integrity of disease-corrected human induced pluripotent stem cells by exome sequencing
| EGAD00001000030 | EGA
Project description:Human induced pluripotent stem cells (iPSCs) - derived mesenchymal stromal cells (iMSCs) are a potentially useful cell type for circumventing ageing-related shortfalls associated with primary mesenchymal or skeletal stromal cells (MSCs/SSCs). To date, the extent of the reflection of ageing-hallmarks in iMSCs differentiated from iPSCs derived from elderly donors remains unclear. In this study, we show that fetal (55 days post conception) femur-derived MSCs and MSCs isolated from aged (60 – 74 years) donors differ in their transcriptome and secretome profile. Yet, iMSCs irrespective of donor age and cell type acquired a rejuvenation gene signature, specifically, INHBE, DNMT3B, POU5F1P1, CDKN1C, GCNT2; also present in pluripotent stem cells but not observed in the parental MSCs. Furthermore, dendrograms generated from the transcriptomes of iMSCs derived from the human embryonic stem cell line H1, fetal and aged MSCs always clustered together with the parental fetal femur-derived MSCs. In addition, these were distinct from MSCs isolated from aged donors when comparing gene ontologies (GOs) related to ageing processes. Critically, in terms of regenerative medicine applications, iMSCs re-acquired a similar secretome (e.g. SERPINE1, SDF-1a, HGF, IL6, IL10, THBS1) to that of the parental fetal MSCs, thus re-enforcing their capabilities of imparting context dependent paracrine signaling.
2019-03-13 | GSE97311 | GEO
Project description:Zinc finger and SCAN domain-containing 10 (Zscan10, also known as Zfp206) encodes a transcription factor that has been reported to be involved in the maintenance of pluripotency in mouse embryonic stem (ES) cells. Here we generated inducible knockout ES cells for Zscan10 using the Cre-loxP system and analyzed its function. We succeeded in establishing Zscan10-null ES cells and confirmed their pluripotency by the generation of chimeric embryos. Our results clearly indicate that Zscan10 is dispensable for the ability of self-renewal and differentiation in ES cells.
2015-12-20 | GSE76143 | GEO
Project description:Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden. Hematopoietic stem cells (HSC) have been sorted out from young and aged steady-state mice, and from recipients transplanted with young and aged bone marrow. Generated iPS and commercially available ES cells were also sorted and analyzed.
2013-03-06 | E-GEOD-44923 | biostudies-arrayexpress