Abstract:
:Mutations in the NADPH oxidase, which is crucial for the respiratory burst in phagocytes, result in chronic granulomatous disease (CGD). The only curative treatment option for CGD patients, who suffer from severe infections, is allogeneic bone marrow transplantation. Over 90% of patients with mutations in the p47phox subunit of the oxidase complex carry the deletion c.75_76delGT (ΔGT). This frequent mutation most likely originates via gene conversion from one of the two pseudogenes NCF1B or NCF1C, which are highly homologous to NCF1 (encodes p47phox) but carry the ΔGT mutation. We applied CRISPR/Cas9 to generate patient-like p47-ΔGT iPSCs for disease modeling. To avoid unpredictable chromosomal rearrangements by CRISPR/Cas9-mediated cleavage in the pseudogenes, we developed a gene-correction approach to specifically target NCF1 but leave the pseudogenes intact. Functional assays revealed restored NADPH oxidase activity and killing of bacteria in corrected phagocytes as well as the specificity of this approach.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Klatt D,Cheng E,Philipp F,Selich A,Dahlke J,Schmidt RE,Schott JW,Büning H,Hoffmann D,Thrasher AJ,Schambach Adoi
10.1016/j.stemcr.2019.08.008subject
Has Abstractpub_date
2019-10-08 00:00:00pages
590-598issue
4issn
2213-6711pii
S2213-6711(19)30302-9journal_volume
13pub_type
杂志文章abstract::Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expressio...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.12.026
更新日期:2017-03-14 00:00:00
abstract::Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem c...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.12.011
更新日期:2021-01-06 00:00:00
abstract::The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed compr...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.05.006
更新日期:2016-07-12 00:00:00
abstract::The transition from naive to primed state of pluripotent stem cells is hallmarked by epithelial-mesenchymal transition, metabolic switch from oxidative phosphorylation to aerobic glycolysis, and changes in the epigenetic landscape. Since these changes are also seen as putative hallmarks of neoplastic cell transformati...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.004
更新日期:2018-03-13 00:00:00
abstract::Neurons differentiated from induced pluripotent stem cells (iPSCs) typically show regular spiking and synaptic activity but lack more complex network activity critical for brain development, such as periodic depolarizations including simultaneous involvement of glutamatergic and GABAergic neurotransmission. We generat...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.05.015
更新日期:2020-07-14 00:00:00
abstract::Cell division is a process by which a mother cell divides into genetically identical sister cells, although sister cells often display considerable diversity. In this report, over 350 sister embryonic stem cells (ESCs) were isolated through a microdissection method, and then expression levels of 48 key genes were exam...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.08.005
更新日期:2013-09-26 00:00:00
abstract::Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regula...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.12.016
更新日期:2017-02-14 00:00:00
abstract::Reprogramming of somatic cells produces induced pluripotent stem cells (iPSCs) that are invaluable resources for biomedical research. Here, we extended the previous transcriptome studies by performing RNA-seq on cells defined by a combination of multiple cellular surface markers. We found that transcriptome changes du...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.04.009
更新日期:2015-06-09 00:00:00
abstract::Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.12.008
更新日期:2018-02-13 00:00:00
abstract::In various vertebrate species, the dorsal aorta (Ao) is the site of specification of adult hematopoietic stem cells (HSCs). It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventr...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.02.004
更新日期:2014-03-27 00:00:00
abstract::Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduce...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.09.008
更新日期:2014-11-11 00:00:00
abstract::Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.11.008
更新日期:2013-12-12 00:00:00
abstract::Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.08.011
更新日期:2018-10-09 00:00:00
abstract::FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.07.010
更新日期:2020-09-08 00:00:00
abstract::Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patien...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.07.015
更新日期:2018-09-11 00:00:00
abstract::Being able to summarize properly your work is not an easy task. But learning the skill of writing a good abstract is very important, as it can open many doors, including the possibility to be selected as a speaker at conferences. As meeting abstract reviewers, here we are writing to give you insights into the abstract...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.11.016
更新日期:2018-12-11 00:00:00
abstract::Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.10.015
更新日期:2017-12-12 00:00:00
abstract::Precise methods for transgene regulation are important to study signaling pathways and cell lineages in biological systems where gene function is often recycled within and across lineages. We engineered a genetic toolset for flexible transgene regulation in these diverse cellular contexts. Specifically, we created an ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.01.013
更新日期:2015-03-10 00:00:00
abstract::Thyroid hormone (TH) transporters are required for the transmembrane passage of TH in target cells. In humans, inactivating mutations in the TH transporter MCT8 cause the Allan-Herndon-Dudley syndrome, characterized by severe neuromuscular symptoms and an abnormal TH serum profile, which is fully replicated in Mct8 kn...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.03.021
更新日期:2018-06-05 00:00:00
abstract::Differentiation of human embryonic stem cells into pancreatic β cells holds great promise for the treatment of diabetes. Recent advances have led to the production of glucose-responsive insulin-secreting cells in vitro, but resulting cells remain less mature than their adult primary β cell counterparts. The barrier(s)...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.11.009
更新日期:2020-01-14 00:00:00
abstract::Primitive erythropoiesis follows a stereotypic developmental program of mesoderm ventralization and internalization, hemangioblast formation and migration, and erythroid lineage specification. Induction of erythropoiesis is inefficient in either ES/iPS cells in vitro or nonhemangioblast cell populations in vivo. Using...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.01.019
更新日期:2014-03-06 00:00:00
abstract::Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.06.010
更新日期:2018-08-14 00:00:00
abstract::Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.01.003
更新日期:2020-02-11 00:00:00
abstract::Molecular mechanisms responsible for the development of human skin epithelial cells are incompletely understood. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSCs) remains poor. Using an approach including RNAi and high-throughput ima...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.08.023
更新日期:2017-10-10 00:00:00
abstract::The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis,...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.07.008
更新日期:2015-08-11 00:00:00
abstract::Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a m...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.03.005
更新日期:2017-05-09 00:00:00
abstract::The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.03.011
更新日期:2018-04-10 00:00:00
abstract::The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiP...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.10.019
更新日期:2018-12-11 00:00:00
abstract::Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreov...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.015
更新日期:2018-03-13 00:00:00
abstract::Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antag...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.08.018
更新日期:2018-10-09 00:00:00