Publications by authors named "Jonghe J"

Understanding the rapidly evolving landscape of single-cell and spatial omic technologies is crucial for advancing biomedical research and drug development. We provide a living review of both mature and emerging commercial platforms, highlighting key methodologies and trends shaping the field. This review spans from foundational single-cell technologies such as microfluidics and plate-based methods to newer approaches like combinatorial indexing; on the spatial side, we consider next-generation sequencing and imaging-based spatial transcriptomics.

View Article and Find Full Text PDF
Article Synopsis
  • Precision medicine relies on understanding genetic variants that cause disease and their effects, exemplified by the von Hippel-Lindau (VHL) gene involved in tumor suppression.
  • VHL mutations are linked to specific types of tumors, like clear cell renal cell carcinoma, necessitating refined methods to assess their consequences.
  • Researchers developed a technique to analyze nearly all single-nucleotide variants in VHL, leading to the identification of key pathogenic variants and enhancing the ability to classify these genetic changes in clinical settings.
View Article and Find Full Text PDF
Article Synopsis
  • Droplet microfluidic methods have improved the efficiency of single-cell sequencing but face challenges like increased background noise and lower RNA capture rates due to the lack of effective cell enrichment strategies.
  • The presented methodology uses fluorescence-activated droplet sorting to isolate droplets containing viable or specific cell types and employs picoinjection for multi-step processes, enhancing gene detection by five times and reducing noise by up to 50%.
  • This approach successfully creates a high-quality molecular atlas of mouse brain development and nascent RNA transcription during organogenesis, and can be adapted for various other droplet-based workflows to achieve cost-effective and precise single-cell profiling.
View Article and Find Full Text PDF
Article Synopsis
  • Biomechanical cues are crucial for embryonic development and cell differentiation, and studying these can reveal how physical stimuli influence gene expression during early mammalian development.
  • By using microfluidic techniques to encapsulate mouse embryonic stem cells, researchers found that Plakoglobin (Jup), a key protein, enhances the network responsible for maintaining naive pluripotency.
  • The study highlights Plakoglobin's role as a mechanosensitive regulator, suggesting that its expression during blastocyst formation in both human and mouse embryos is vital for understanding cell fate transitions influenced by the physical environment.
View Article and Find Full Text PDF

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models.

View Article and Find Full Text PDF

Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis.

View Article and Find Full Text PDF

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization.

View Article and Find Full Text PDF

(1) Background: There is a need for a brief assessment of cognitive function, both in patient care and scientific research, for which the Montreal Cognitive Assessment (MoCA) is a psychometrically reliable and valid tool. However, fine-grained normative data allowing for adjustment for age, education, and/or sex are lacking, especially for its Memory Index Score (MIS). (2) Methods: A total of 820 healthy individuals aged 18-91 (366 men) completed the Dutch MoCA (version 7.

View Article and Find Full Text PDF
Article Synopsis
  • Traditional single-cell transcriptome sequencing only captures a limited portion of transcripts by focusing on polyadenylated RNA, missing many important non-coding and non-polyadenylated transcripts.
  • The new VASA-seq method allows for the analysis of the entire transcriptome in single cells by fragmenting and tailing all RNA after cell lysis, and it works with both plate-based and droplet microfluidic systems.
  • Applying VASA-seq to over 30,000 single cells in developing mouse embryos revealed key findings such as novel cell type markers, insights into blood maturation trajectories, and extensive alternative splicing during development.
View Article and Find Full Text PDF

Purpose: Early delirium detection in nursing home residents is vital to prevent adverse outcomes. Despite the potential of structured delirium screening tools to enhance delirium detection, they are rarely used in nursing homes. To promote delirium screening tools in nursing homes, they should be easy to integrate into the daily routine of care workers.

View Article and Find Full Text PDF

Background: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline.

Objectives: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium.

View Article and Find Full Text PDF

The development of mouse embryos can be partially recapitulated by combining embryonic stem cells (ESCs), trophoblast stem cells (TS), and extra-embryonic endoderm (XEN) stem cells to generate embryo-like structures called ETX embryos. Although ETX embryos transcriptionally capture the mouse gastrula, their ability to recapitulate complex morphogenic events such as gastrulation is limited, possibly due to the limited potential of XEN cells. To address this, we generated ESCs transiently expressing transcription factor Gata4, which drives the extra-embryonic endoderm fate, and combined them with ESCs and TS cells to generate induced ETX embryos (iETX embryos).

View Article and Find Full Text PDF

Background/aims: Research guidelines on predicting and diagnosing Alzheimer's disease (AD) acknowledge cerebrospinal fluid (CSF) levels as pivotal biomarkers. We studied the usefulness of CSF biomarkers in the diagnostic workup of patients in a geriatric outpatient memory clinic of a community-based hospital, attempted to determine a cutoff age for the use of CSF biomarkers in this group of patients, and compared the total τ/Aβ ratio as an alternative CSF diagnostic rule with the usual rules for interpreting CSF levels.

Methods: This was a prospective study of consecutively referred patients.

View Article and Find Full Text PDF

We investigated preserved episodic recognition memory based on incidental learning of visual associations in Alzheimer's disease (AD). In a cross-sectional design, we analyzed episodic memory score profiles of patients with amnestic mild cognitive impairment (a-MCI) ( = 42) or mild AD ( = 19) who had hippocampal atrophy, and healthy elderly controls ( = 43). The Visual Association Test-Extended served as a measure of episodic memory.

View Article and Find Full Text PDF

Mammalian blastocysts comprise three distinct cell lineages essential for development beyond implantation: the pluripotent epiblast, which generates the future embryo, and surrounding it the extra-embryonic primitive endoderm and the trophectoderm tissues. Embryonic stem cells can reintegrate into embryogenesis but contribute primarily to epiblast lineages. Here, we show that mouse embryonic stem cells cultured under extended pluripotent conditions (EPSCs) can be partnered with trophoblast stem cells to self-organize into blastocyst-like structures with all three embryonic and extra-embryonic lineages.

View Article and Find Full Text PDF

Background/aims: The available episodic memory tests are not specifically constructed to examine older subjects. Their use in outpatient memory clinics may result in aborted test administration. We used a strict adherence to the test protocol in cognitively healthy, amnestic mild cognitive impairment (aMCI), and Alzheimer's disease dementia subjects to assess the possibility of preventing this.

View Article and Find Full Text PDF

Objectives: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium.

View Article and Find Full Text PDF

Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages.

View Article and Find Full Text PDF

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer's disease (AD), this may support health care to be more closely aligned with patients' memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects.

View Article and Find Full Text PDF

Objective: Given the hazards of knowledge about performance validity tests (PVTs) being proliferated among the general public, there is a continuous need to develop new PVTs. The purpose of these studies was to validate the newly developed Visual Association Test-Extended (VAT-E).

Method: The VAT-E consists of 24 pairs of line drawings; it is partly based on Green's Word Memory Test (WMT) paradigm.

View Article and Find Full Text PDF

Low-cost shotgun DNA sequencing is transforming the microbial sciences. Sequencing instruments are so effective that sample preparation is now the key limiting factor. Here, we introduce a microfluidic sample preparation platform that integrates the key steps in cells to sequence library sample preparation for up to 96 samples and reduces DNA input requirements 100-fold while maintaining or improving data quality.

View Article and Find Full Text PDF

Objectives: To evaluate the prevalence of cognitive impairment (CI), including mild CI and dementia, in elderly patients with syncope and unexplained falls. In this population, we compared the use of the Mini-Mental State Examination (MMSE) with a cognitive screening test that assesses executive dysfunction typical of subcortical (vascular) CI, that is, the Montreal Cognitive Assessment (MoCA).

Design: Observational cohort study.

View Article and Find Full Text PDF

Background And Aim: Data showing the usefulness of MRI to improve the accuracy of the diagnostic process in cognitive disorders were derived from studies in tertiary referral centers. MRI is widely used as a diagnostic tool in everyday practice, but it is unknown what the actual added value of MRI is. We studied the usefulness of MRI in the diagnostic process by measuring the change of confidence of the physician.

View Article and Find Full Text PDF