Abstract:
:A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Le Belle JE,Sperry J,Ngo A,Ghochani Y,Laks DR,López-Aranda M,Silva AJ,Kornblum HIdoi
10.1016/j.stemcr.2014.09.004subject
Has Abstractpub_date
2014-11-11 00:00:00pages
725-34issue
5issn
2213-6711pii
S2213-6711(14)00289-6journal_volume
3pub_type
杂志文章abstract::Self-renewal potential and multipotency are hallmarks of a stem cell. It is generally accepted that acquisition of such stemness requires rejuvenation of somatic cells through reprogramming of their genetic and epigenetic status.We show here that a simple block of cell differentiation is sufficient to induce and maint...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.09.012
更新日期:2015-11-10 00:00:00
abstract::Pluripotent cells emanate from the inner cell mass (ICM) of the blastocyst and when cultivated under optimal conditions immortalize as embryonic stem cells (ESCs). The fundamental mechanism underlying ESC derivation has, however, remained elusive. Recently, we have devised a highly efficient approach for establishing ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.08.006
更新日期:2017-10-10 00:00:00
abstract::Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of func...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.10.011
更新日期:2018-12-11 00:00:00
abstract::High-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained h...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.09.007
更新日期:2017-11-14 00:00:00
abstract::Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independe...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.01.013
更新日期:2016-03-08 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::The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functi...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.03.023
更新日期:2017-05-09 00:00:00
abstract::Pig embryonic stem cells (pESCs) have been considered an important candidate for preclinical research on human therapies. However, the lack of understanding of pig pluripotent networks has hampered establishment of authentic pESCs. Here, we report that FGF2, ACTVIN, and WNT signaling are essential to sustain pig pluri...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.05.028
更新日期:2019-07-09 00:00:00
abstract::We have developed an improved episomal vector system for efficient generation of integration-free induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells. More recently, we reported that the use of an optimized CRISPR-Cas9 system together with a double-cut donor increases homology-directed repai...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.04.013
更新日期:2018-06-05 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::Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation, but how lncRNA is integrated with known transcriptional regulatory network is poorly understood. Here, we utilize human definitive endoderm differentiation as a model system and decipher the function...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.07.014
更新日期:2020-09-08 00:00:00
abstract::Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs and how this information is encoded is unclear. To better understand how this information is stored, we performed RNA sequencing on HSC populatio...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.03.005
更新日期:2020-04-14 00:00:00
abstract::We established two human embryonic stem cell (hESC) lines with a GGGGCC expansion in the C9orf72 gene (C9), and compared them with haploidentical and unrelated C9 induced pluripotent stem cells (iPSCs). We found a marked difference in C9 methylation between the cells. hESCs and parental fibroblasts are entirely unmeth...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.09.011
更新日期:2016-11-08 00:00:00
abstract::The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with r...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.08.002
更新日期:2016-09-13 00:00:00
abstract::The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 comple...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.019
更新日期:2018-03-13 00:00:00
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 ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.08.008
更新日期:2019-10-08 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::Genetic changes in human pluripotent stem cells (hPSCs) gained during culture can confound experimental results and potentially jeopardize the outcome of clinical therapies. Particularly common changes in hPSCs are trisomies of chromosomes 1, 12, 17, and 20. Thus, hPSCs should be regularly screened for such aberration...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.10.003
更新日期:2016-11-08 00:00:00
abstract::Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed di...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.08.014
更新日期:2016-10-11 00:00:00
abstract::Cardiomyocytes derived from human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, disease modeling, and drug discovery, all of which require enriched cardiomyocytes, ideally ones with mature phenotypes. However, current methods are typically performed in 2D environments that produ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.06.002
更新日期:2014-08-12 00:00:00
abstract::Stem Cell Reports frequently receives manuscripts dealing with the topic of cancer stem cells. Many of the submissions on this topic have major shortcomings in their content or limits to the conclusions that can be drawn from the results presented. The purpose of this Commentary is to highlight some of the underlying ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.01.011
更新日期:2020-02-11 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 environment surrounding stem cells has the ability to elicit profound, heritable epigenetic changes orchestrated by multiple epigenetic mechanisms, which can be modulated by the level of specific metabolites. In this review, we highlight the significance of metabolism in regulating stem cell homeostasis, cell stat...
journal_title:Stem cell reports
pub_type: 杂志文章,评审
doi:10.1016/j.stemcr.2019.09.003
更新日期:2019-10-08 00:00:00
abstract::We earlier showed that outside-in integrin signaling through POSTN-ITGAV interaction plays an important role in regulating adult hematopoietic stem cell (HSC) quiescence. Here, we show that Itgav deletion results in increased frequency of phenotypic HSCs in fetal liver (FL) due to faster proliferation. Systemic deleti...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.06.022
更新日期:2020-08-11 00:00:00
abstract::Tight regulation of the balance between self-renewal and differentiation of neural stem cells is crucial to assure proper neural development. In this context, Notch signaling is a well-known promoter of stemness. In contrast, the bifunctional brain-enriched microRNA miR-9/9(∗) has been implicated in promoting neuronal...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.06.008
更新日期:2016-08-09 00:00:00
abstract::In this article, Scott describes how a new counseling profession could support clinical sites and patients enrolling in stem cell clinical trials. A possible model is proposed, along with a curriculum that would provide counselors with the tools to address challenges facing the clinical stem cell field. Finally, a can...
journal_title:Stem cell reports
pub_type: 信件
doi:10.1016/j.stemcr.2014.10.016
更新日期:2015-01-13 00:00:00
abstract::Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.002
更新日期:2018-02-13 00:00:00
abstract::Mammalian haploid embryonic stem cells (haESCs) hold great promise for functional genetic studies and forward screening. However, all established haploid cells are prone to spontaneous diploidization during long-term culture, rendering application challenging. Here, we report a genome-wide loss-of-function screening t...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.11.016
更新日期:2021-01-12 00:00:00
abstract::Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepat...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.10.016
更新日期:2015-12-08 00:00:00