Comparison of American mink embryonic stem and induced pluripotent stem cell transcriptomes

BACKGROUND: Recently fibroblasts of many mammalian species have been reprogrammed to pluripotent state using overexpression of several transcription factors. This technology allows production of induced pluripotent stem (iPS) cells with properties similar to embryonic stem (ES) cells. The completeness of reprogramming process is well studied in such species as mouse and human but there is not enough data on other species. We produced American mink (Neovison vison) ES and iPS cells and compared these cells using transcriptome analysis. RESULTS: We report the generation of 10 mink ES and 22 iPS cell lines. The majority of the analyzed cell lines had normal diploid chromosome number. The only ES cell line with XX chromosome set had both X-chromosomes in active state that is characteristic of pluripotent cells. The pluripotency of ES and iPS cell lines was confirmed by formation of teratomas with cell types representing all three germ layers. Transcriptome analysis of mink embryonic fibroblasts (EF), two ES and two iPS cell lines allowed us to identify 11831 assembled contigs which were annotated. These led to a number of 6891 unique genes. Of these 3201 were differentially expressed between mink EF and ES cells. We analyzed expression levels of these genes in iPS cell lines. This allowed us to show that 80% of genes were correctly reprogrammed in iPS cells, whereas approximately 6% had an intermediate expression pattern, about 7% were not reprogrammed and about 5% had a "novel" expression pattern. We observed expression of pluripotency marker genes such as Oct4, Sox2 and Rex1 in ES and iPS cell lines with notable exception of Nanog. CONCLUSIONS: We had produced and characterized American mink ES and iPS cells. These cells were pluripotent by a number of criteria and iPS cells exhibited effective reprogramming. Interestingly, we had showed lack of Nanog expression and consider it as a species-specific feature

An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic stem and progenitor cells induces a preleukemic state in transplanted immunodeficient NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolve into BCP-ALL with spontaneously acquired Cyclin Dependent Kinase Inhibitor 2 A (CDKN2A) deletions, as commonly observed in primary human BCP-ALL. CRISPR mediated gene silencing of CDKN2A in primary human CD34+ cells transduced with activated IL7RA results in robust development of BCP-ALLs in-vivo. Thus, we demonstrate that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.This work was supported by the Israel Science Foundation (# 1178/12 to S.I.), Children with Cancer (UK) (S.I. and T.E.), Swiss Bridge Foundation (S.I.), WLBH Foundation (S.I.), Waxman Cancer Research Foundation (S.I.), US–Israel Binational Science Foundation, Israeli health ministry ERA-NET program (#CANCER11-FP-127 to S.I.), Hans Neufeld Stiftung, the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope (S.I. grants # 00161), the Nevzlin Genomic Center for Precision Medicine in Schneider Children’s Medical Center of Israel, The European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813091 (S.I.) and the Israel Childhood Cancer Foundation (S.I.). I.G. was partially supported by Israeli ministry of Immigrant Absorption.info:eu-repo/semantics/publishedVersio

Language and sociability: insights from Williams syndrome

One of the most compelling features of Williams syndrome (WS) is the widely reported excessive sociability, accompanied by a relative proficiency in expressive language, which stands in stark contrast with significant intellectual and nonverbal impairments. It has been proposed that the unique language skills observed in WS are implicated in the strong drive to interact and communicate with others, which has been widely documented in WS. Nevertheless, this proposition has yet to be empirically examined. The present study aimed at investigating the relationship between a brain index of language processing and judgments of approachability of faces, as a proxy for sociability, in individuals with WS as contrasted to typical controls. Results revealed a significant and substantial association between the two in the WS, but not in the control group, supporting the hitherto untested notion that language use in WS might be uniquely related to their excessive social drive

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity

Alcohol expectancy cognitions: Psychophysiological perspective

Considerable evidence indicates that the expectations individuals hold about the effects of alcohol determine, to a degree, the amount of alcohol they drink. However, the bulk of this evidence was acquired using verbally-based measures of expectancy. The present study sought to extend the validation network by utilizing an electrophysiological measure -- the P300 component of the Event Related Potentials (ERPs) -- which is thought to index fundamental neurophysiological processes sensitive to expectancy.Previous research has demonstrated that, when presented with various outcomes of alcohol consumption, heavier drinkers endorse statements that assert positive and arousing effects of alcohol, while lighter drinkers endorse sedating and negative effects of alcohol. Given the sensitivity of the P300 to violation of subjective expectancies, it was hypothesized that P300 amplitude elicited by stimuli violating one\u27s alcohol expectancies (e.g., statements describing sedating effects of alcohol for individuals with high positive expectancies) would be correlated with the participants\u27 alcohol expectancies measured by traditional self-report measures.Participants were presented with statements reflecting a wide range of alcohol outcome effects, which either violated or confirmed the participant\u27s own set of alcohol expectancies, while the ERPs evoked by these stimuli were recorded. As predicted, the P 300 amplitude elicited by negative alcohol expectancy stimuli was positively correlated with the degree of endorsement of positive/arousing expectancies on the self-report measure. That is, the higher the individual\u27s positive/arousing expectancies, the larger the P300 elicited by stimuli asserting the negative effects of alcohol. There was no significant correlation, however, between P300 amplitude elicited by positive alcohol expectancy stimuli and the degree of endorsement of negative/sedating expectancies on the self-report measure.In sum, variations in the amplitude of the P300 were consistent with the model of Alcohol Expectancies: Namely, words imputing negative/sedating effects of alcohol elicited a large P300 in individuals with high but not low positive alcohol expectancies. By indexing the brain\u27s electrophysiological response sensitive to expectancy violations, these findings demonstrate concordance between verbal measures of alcohol expectancies, which by their very nat ure are introspective, and a psychophysiological index of expectancy thought to operate automatically and to be independent of overt responding

The P300 as an Electrophysiological Probe of Alcohol Expectancy

Language-based measures indicate that alcohol expectancies influence alcohol consumption. To relate these measures to brain actions that precede verbal output, the P300 component of the Event-related potentials (ERPs) was used to detect violations of individually held alcohol expectancies. As predicted, P300 amplitude elicited by negative alcohol expectancy stimuli was positively correlated with endorsement of positive/arousing alcohol expectancies on the language-based measures, such that the higher an individual\u27s positive/arousing expectancies, the larger was the P300 elicited by negative alcohol expectancy stimuli. These results demonstrated concordance between language-based measures of alcohol expectancies and electrophysiological probes of expectancy. While it remains unknown whether these expectancy processes are integral to decision pathways that influence consumption, these findings suggest that such processing can occur very quickly outside of conscious deliberation

Resting State Functional Networks in 1-to-3-year-old Typically Developing Children

Major brain functional networks in young children, generated with a 20-dimensional ICA of resting-state fMRI data acquired during natural slee

Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder.

ImportanceConverging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.ObjectiveTo investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).Design, setting, and participantsCross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.Main outcomes and measuresStatistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.ResultsRelative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.Conclusions and relevanceAdolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD