Generation of IPi002-A/B/C human induced pluripotent stem cell lines from MARCH amniotic fluid cells.

Human induced pluripotent stem cells (hiPSCs) have become a revolutionary tool in biomedical research due to their unique in vitro properties and fate versatility. They offer insights into development or genetic disorders, facilitate drug discovery and hold promise for regenerative medicine. Here we generated three hiPSC cells - IPi002-A/B/C - from primary amniotic fluid cells (AFCs) obtained via amniocentesis for the prenatal diagnosis of MARCH syndrome: Multinucleated neurons, Anhydramnios, Renal dysplasia, Cerebellar hypoplasia, and Hydranencephaly.

Generation of IPi001-A/B/C human induced pluripotent stem cell lines from healthy amniotic fluid cells.

Human induced Pluripotent Stem Cells (hiPSCs) represent an invaluable source of primary cells to investigate development, establish cell and disease models, provide material for regenerative medicine and allow more physiological high-content screenings. Here, we generated three healthy hiPSC control lines - IPi001-A/B/C - from primary amniotic fluid cells (AFCs), an infrequently used source of cells, which can be readily obtained from amniocentesis for the prenatal diagnosis of numerous genetic disorders. These AFCs were reprogrammed by non-integrative viral transduction.

Successful 3D imaging of cleared biological samples with light sheet fluorescence microscopy.

In parallel with the development of tissue-clearing methods, over the last decade, light sheet fluorescence microscopy has contributed to major advances in various fields, such as cell and developmental biology and neuroscience. While biologists are increasingly integrating three-dimensional imaging into their research projects, their experience with the technique is not always up to their expectations. In response to a survey of specific challenges associated with sample clearing and labeling, image acquisition, and data analysis, we have critically assessed the recent literature to characterize the difficulties inherent to light sheet fluorescence microscopy applied to cleared biological samples and to propose solutions to overcome them.

Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency.

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients.

Three-dimensional molecular cartography of human cerebral organoids revealed by double-barcoded spatial transcriptomics.

Spatially resolved transcriptomics is revolutionizing our understanding of complex tissues, but scaling these approaches to multiple tissue sections and three-dimensional tissue reconstruction remains challenging and cost prohibitive. In this work, we present a low-cost strategy for manufacturing molecularly double-barcoded DNA arrays, enabling large-scale spatially resolved transcriptomics studies. We applied this technique to spatially resolve gene expression in several human brain organoids, including the reconstruction of a three-dimensional view from multiple consecutive sections, revealing gene expression heterogeneity throughout the tissue.

Human Brain Organoids-on-Chip: Advances, Challenges, and Perspectives for Preclinical Applications.

There is an urgent need for predictive in vitro models to improve disease modeling and drug target identification and validation, especially for neurological disorders. Cerebral organoids, as alternative methods to in vivo studies, appear now as powerful tools to decipher complex biological processes thanks to their ability to recapitulate many features of the human brain. Combining these innovative models with microfluidic technologies, referred to as brain organoids-on-chips, allows us to model the microenvironment of several neuronal cell types in 3D.

iPSCs derived from infertile men carrying complex genetic abnormalities can generate primordial germ-like cells.

Despite increasing insight into the genetics of infertility, the developmental disease processes remain unclear due to the lack of adequate experimental models. The advent of induced pluripotent stem cell (iPSC) technology has provided a unique tool for in vitro disease modeling enabling major advances in our understanding of developmental disease processes. We report the full characterization of complex genetic abnormalities in two infertile patients with either azoospermia or XX male syndrome and we identify genes of potential interest implicated in their infertility.

[Chimeric embryos and pseudo-embryos: An alternative to human embryos for research].

The study of human development is essential to further our knowledge and to improve our therapeutic strategies in the fields of reproductive and regenerative medicine. Given the limited access to supernumerary embryos and the prohibition on creating new ones for research, two alternative strategies can be proposed to study human embryonic development. The first is to create pseudo-embryos or blastoids.

Fanning the Flames of Passion: A Develop Mindset Predicts Strategy-Use Intentions to Cultivate Passion.

College students are encouraged to major in subjects they are passionate about but less often advised about what to do when passion is low. What self-regulatory strategies do students use to up-regulate their passion toward their subjects, and how might they be oriented toward using such effective strategies? Three studies examined how the belief that passion is developed - a "develop" mindset - relates to students' intentions to use strategies to actively grow their passion. The more strongly students endorsed a develop mindset, the more of these "cultivation strategies" they reported using, and in turn, the larger their increase in reported passion toward their subject majors (Study 1).

Long Term Gene Expression in Human Induced Pluripotent Stem Cells and Cerebral Organoids to Model a Neurodegenerative Disease.

Human brain organoids (mini-brains) consist of self-organized three-dimensional (3D) neural tissue which can be derived from reprogrammed adult cells and maintained for months in culture. These 3D structures manifest substantial potential for the modeling of neurodegenerative diseases and pave the way for personalized medicine. However, as these 3D brain models can express the whole human genetic complexity, it is critical to have access to isogenic mini-brains that only differ in specific and controlled genetic variables.

Proof-of-Concept Study of Drug Brain Permeability Between in Vivo Human Brain and an in Vitro iPSCs-Human Blood-Brain Barrier Model.

The development of effective central nervous system (CNS) drugs has been hampered by the lack of robust strategies to mimic the blood-brain barrier (BBB) and cerebrovascular impairments in vitro. Recent technological advancements in BBB modeling using induced pluripotent stem cells (iPSCs) allowed to overcome some of these obstacles, nonetheless the pertinence for their use in drug permeation study remains to be established. This mandatory information requires a cross comparison of in vitro and in vivo pharmacokinetic data in the same species to avoid failure in late clinical drug development.

Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes.

Human mini-brains (MB) are cerebral organoids that recapitulate in part the complexity of the human brain in a unique three-dimensional in vitro model, yielding discrete brain regions reminiscent of the cerebral cortex. Specific proteins linked to neurodegenerative disorders are physiologically expressed in MBs, such as APP-derived amyloids (Aβ), whose physiological and pathological roles and interactions with other proteins are not well established in humans. Here, we demonstrate that neuroectodermal organoids can be used to study the Aβ accumulation implicated in Alzheimer's disease (AD).

The Influence of Effortful Thought and Cognitive Proficiencies on the Conjunction Fallacy: Implications for Dual-Process Theories of Reasoning and Judgment.

Human judgment often violates normative standards, and virtually no judgment error has received as much attention as the conjunction fallacy. Judgment errors have historically served as evidence for dual-process theories of reasoning, insofar as these errors are assumed to arise from reliance on a fast and intuitive mental process, and are corrected via effortful deliberative reasoning. In the present research, three experiments tested the notion that conjunction errors are reduced by effortful thought.

Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies.

Despite progress in human reproductive biology, the cause of male infertility often remains unknown, due to the lack of appropriate and convenient in vitro models of meiosis. Induced pluripotent stem cells (iPSCs) derived from the cells of infertile patients could provide a gold standard model for generating primordial germ cells and studying their development and the process of spermatogenesis. We report the characterization of a complex chromosomal rearrangement (CCR) in an azoospermic patient, and the successful generation of specific-iPSCs from PBMC-derived erythroblasts.

Culture and decision making.

The study of culture and decision making addresses variations in how and why people from different cultures sometimes tend to decide differently. This review is organized around what is intended to be a comprehensive analysis of the distinct fundamental questions that people must answer in the process of making virtually all real-life decisions. Our emphasis was on recent developments as well as identifying important yet neglected topics (e.

Regulating Emotions during Difficult Multiattribute Decision Making: The Role of Pre-Decisional Coherence Shifting.

Almost all real-life decisions entail attribute conflict; every serious choice alternative is better than its competitors on some attribute dimensions but worse on others. In pre-decisional "coherence shifting," the decision maker gradually softens that conflict psychologically to the point where one alternative is seen as dominant over its competitors, or nearly so. Specifically, weaknesses of the eventually chosen alternative come to be perceived as less severe and less important while its strengths seem more desirable and significant.

Understanding and Reducing Inconsistency in Seatbelt-Use Decisions: Findings from a Cardinal Decision Issue Perspective.

This article has two aims. The first is to present results that partly explain why some automobile drivers choose to use their seatbelts only part time, thereby exposing themselves to unnecessary risk. The second is to offer and illustrate the "cardinal decision issue perspective"((1)) as a tool for guiding research and development efforts that focus on complex real-life decision behaviors that can entail wide varieties of risk, including but not limited to inconsistent seatbelt use.

Creating conditions for the success of the French industrial advanced therapy sector.

Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model.

Background: Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.

Design And Methods: We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin.

Examining determinants of self management behaviors in patients with diabetes: an application of the Theoretical Model of Effortful Decision Making and Enactment.

Objective: This study examined determinants of self-monitoring of blood glucose (SMBG) in patients with diabetes based on a theoretical model. The model focuses on two equally important components of the decision process within a single framework: (1) making a decision and (2) enacting the decision.

Methods: Diabetes patients with HbA1c >7% and requiring insulin therapy were recruited from a southeastern Michigan healthcare system.

Partial reversal of the methylation pattern of the X-linked gene HUMARA during hematopoietic differentiation of human embryonic stem cells.

Human embryonic stem cells (hESCs) can be induced to differentiate towards hematopoiesis with high efficiency. In this work, we analyzed the methylation status of the X-linked HUMARA (human androgen receptor) gene in hematopoietic cells derived from hESC line H9 before and after induction of hematopoietic differentiation. All passages of H9 and H9-derived hematopoietic cells displayed homogenous methylation pattern with disappearance of the same allele upon HpaII digestion.