Abstract：
:Members of the Fanconi anemia (FA) protein family are involved in multiple cellular processes including response to DNA damage and oxidative stress. Here we show that a major FA protein, Fancd2, plays a role in mitochondrial biosynthesis through regulation of mitochondrial translation. Fancd2 interacts with Atad3 and Tufm, which are among the most frequently identified components of the mitochondrial nucleoid complex essential for mitochondrion biosynthesis. Deletion of Fancd2 in mouse hematopoietic stem and progenitor cells (HSPCs) leads to increase in mitochondrial number, and enzyme activity of mitochondrion-encoded respiratory complexes. Fancd2 deficiency increases mitochondrial protein synthesis and induces mitonuclear protein imbalance. Furthermore, Fancd2-deficient HSPCs show increased mitochondrial respiration and mitochondrial reactive oxygen species. By using a cell-free assay with mitochondria isolated from WT and Fancd2-KO HSPCs, we demonstrate that the increased mitochondrial protein synthesis observed in Fancd2-KO HSPCs was directly linked to augmented mitochondrial translation. Finally, Fancd2-deficient HSPCs are selectively sensitive to mitochondrial translation inhibition and depend on augmented mitochondrial translation for survival and proliferation. Collectively, these results suggest that Fancd2 restricts mitochondrial activity through regulation of mitochondrial translation, and that augmented mitochondrial translation and mitochondrial respiration may contribute to HSC defect and bone marrow failure in FA.
journal_name
Stem Cell Resjournal_title
Stem cell researchauthors
Chatla S,Du W,Wilson AF,Meetei AR,Pang Qdoi
10.1016/j.scr.2019.101550subject
Has Abstractpub_date
2019-10-01 00:00:00pages
101550eissn
1873-5061issn
1876-7753pii
S1873-5061(19)30180-1journal_volume
40pub_type
杂志文章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：OBJECTIVE:Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2012.10.002
更新日期：2013-01-01 00:00:00
abstract：:A DAND5-control human iPSC line was generated from the urinary cells of a phenotypically normal donor. Exfoliated renal epithelial (RE) cells were collected and reprogrammed into iPSCs using Sendai virus reprogramming system. The pluripotency, in vitro differentiation potential, karyotype stability, and the transgene-...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2018.04.015
更新日期：2018-05-01 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：: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：: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：:OCT4 is a highly conserved gene and plays an important role during early embryonic development and differentiation. Similar to human OCT4, mouse Oct4 gene generates variants. Oct4A is a master regulator of self-renewal in pluripotent stem cells. In this study, we have identified a novel Oct4 spliced variant, designate...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2012.04.004
更新日期：2012-09-01 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：:Understanding the complex mechanisms that govern the fate decisions of human embryonic stem cells (hESCs) is fundamental to their use in cell replacement therapies. The progress of dissecting these mechanisms will be facilitated by the availability of robust high-throughput screening assays on hESCs. In this study, we...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2010.04.006
更新日期：2010-09-01 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：:Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of esta...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.05.003
更新日期：2016-07-01 00:00:00
abstract：:GADD45A is a DNA damage and stressful growth arrest inducible protein, also it is shown to a be tumor suppressor gene and a chromatin relaxer associated with opening chromatin during the somatic reprogramming. However, its role in human embryonic stem cells and human embryonic stem cell modeled development has been me...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.102090
更新日期：2020-12-01 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：:Adult skeletal muscle regeneration relies on the activity of satellite cells residing in the skeletal muscle niche. However, systemic and intrinsic factors decrease the myogenic differentiation potential of satellite cells thereby impairing muscle regeneration. Here we present data showing that late passage C2C12 myob...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2017.11.018
更新日期：2018-01-01 00:00:00
abstract：:The KCL017 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting splicing site of the VHL gene encoding von Hippel-Lindau tumor suppressor E3 ubiquitin protein ligase (676+3A>T). The ICM was isolated using laser microsurgery and plated on γ...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2016.01.013
更新日期：2016-03-01 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
abstract：:Skin fibroblasts were obtained from four patients with Williams-Beuren syndrome (WBS) carrying the typical 1.5 Mb or 1.8 Mb deletion at the 7q11.23 genomic region. Induced pluripotent stem cells (iPSCs) were generated by retroviral infection of fibroblasts with polycystronic vectors. The generated iPSC clones ESi059A,...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.102087
更新日期：2020-12-01 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：: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：:The purpose of this study is to establish a murine embryonic stem cell (mESC) line for isolation of functional ventricular cardiomyocytes (VCMs) and then to characterize the derived VCMs. By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we g...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2011.08.004
更新日期：2012-01-01 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：: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：: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：:Crumbs homologue 1 (CRB1) mutations have been found in retinitis pigmentosa (RP) patients lead to severe retinal dystrophies. The human induced pluripotent stem (iPS) cell line CSUASOi003-A derived from peripheral blood mononuclear cells (PBMCs) of a patient carrying two heterozygous mutations (2249G>A p.G750D and c.2...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.101742
更新日期：2020-04-01 00:00:00
abstract：:The peptide hormone insulin produced by pancreatic β-cells undergoes post-transcriptional processing before secretion. In particular, C-peptide is cleaved from pro-insulin to generate mature insulin. Here, we introduce a C-peptide-mCherry human iPSC line (HMGUi001-A-8). The line was generated by CRISPR/Cas9 mediated h...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.102126
更新日期：2020-12-16 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：: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：:The discovery of the Ten-Eleven Translocation (TET) protein family was initiated by the identification of the MLL partner TET1, and of mutations in the TET2 gene in hematological malignancies including myeloproliferative neoplasms (MPN). TET1, 2 and 3 proteins hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcy...
journal_title：Stem cell research
pub_type： 杂志文章
doi：10.1016/j.scr.2020.101755
更新日期：2020-04-01 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
