Joep Beumer
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View article: Human gut evolution: insights from stem cell models and single-cell genomics
Human gut evolution: insights from stem cell models and single-cell genomics Open
The gastrointestinal (GI) tract evolved in response to dietary changes and pathogen exposures that varied throughout history. As a major interface between the host and environment, the GI epithelia have evolved specialized barrier and immu…
View article: Recent evolution of the developing human intestine affects metabolic and barrier functions
Recent evolution of the developing human intestine affects metabolic and barrier functions Open
Diet, microbiota, and other exposures make the intestinal epithelium a nexus for evolutionary change; however, little is known about genomic changes associated with adaptation to a distinctly human environment. In this work, we interrogate…
View article: Modeling host-microbe interactions in immunocompetent engineered human gut tissues
Modeling host-microbe interactions in immunocompetent engineered human gut tissues Open
The intestinal mucosal barrier contains microbial organisms within the lumen while preserving the ability to absorb nutrients. Dietary, microbial, and other exposures shaped human barrier evolution and continue to impact disease susceptibi…
View article: An integrated transcriptomic cell atlas of human endoderm-derived organoids
An integrated transcriptomic cell atlas of human endoderm-derived organoids Open
Human pluripotent stem cells and tissue-resident fetal and adult stem cells can generate epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. Here, we integrate single-cell tr…
View article: A comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine
A comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine Open
Nuclear receptors (NRs) are widely expressed transcription factors that bind small, lipophilic compounds and regulate diverse biological processes. In the small intestine, NRs are known to act as sensors that control transcriptional respon…
View article: Description and functional validation of human enteroendocrine cell sensors
Description and functional validation of human enteroendocrine cell sensors Open
Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including the incretins glucagon-like peptide 1 (GLP-1) and gastric inhibitory protein (GIP), which regulate multiple physiolo…
View article: Hallmarks of stemness in mammalian tissues
Hallmarks of stemness in mammalian tissues Open
All adult tissues experience wear and tear. Most tissues can compensate for cell loss through the activity of resident stem cells. Although the cellular maintenance strategies vary greatly between different adult (read: postnatal) tissues,…
View article: Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites
Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites Open
Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate mod…
View article: An integrated transcriptomic cell atlas of human endoderm-derived organoids
An integrated transcriptomic cell atlas of human endoderm-derived organoids Open
Human stem cells can generate complex, multicellular epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. These tissues, also called organoids, can be derived from pluripotent…
View article: SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models
SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models Open
SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and inste…
View article: Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models
Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models Open
Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing …
View article: Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer
Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer Open
SUMMARY Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors and poorly-differentiated carcinomas. Treatment options for patients with NENs are limited, in part due to lack of accurate models. To address this …
View article: Differentiation and CRISPR-Cas9-mediated genetic engineering of human intestinal organoids
Differentiation and CRISPR-Cas9-mediated genetic engineering of human intestinal organoids Open
Intestinal organoids are three-dimensional cultures that resemble key aspects of the epithelium of origin. Here, we describe how to differentiate human small intestinal organoids by combining growth media variations and genetic engineering…
View article: BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states
BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states Open
Intestinal epithelial cells derive from stem cells at the crypt base and travel along the crypt-villus axis to die at the villus tip. The two dominant villus epithelial cell types, absorptive enterocytes and mucous-secreting goblet cells, …
View article: A turquoise fluorescence lifetime-based biosensor for quantitative imaging of intracellular calcium
A turquoise fluorescence lifetime-based biosensor for quantitative imaging of intracellular calcium Open
The most successful genetically encoded calcium indicators (GECIs) employ an intensity or intensiometric readout. Despite a large calcium-dependent change in fluorescence intensity, the quantification of calcium concentrations with GECIs i…
View article: A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses
A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses Open
Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, le…
View article: The Organoid Platform: Promises and Challenges as Tools in the Fight against COVID-19
The Organoid Platform: Promises and Challenges as Tools in the Fight against COVID-19 Open
Many pathogenic viruses that affect man display species specificity, limiting the use of animal models. Studying viral biology and identifying potential treatments therefore benefits from the development of in vitro cell systems that close…
View article: Additional file 20 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Additional file 20 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease Open
Additional file 20. Table S19
View article: Additional file 4 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Additional file 4 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease Open
Additional file 4. Table S4