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Article
BEHAV3D: a 3D live imaging platform for comprehensive analysis of engineered T cell behavior and tumor response
Modeling immuno-oncology by using patient-derived material and immune cell co-cultures can advance our understanding of immune cell tumor targeting in a patient-specific manner, offering leads to improve cellu...
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Article
Open AccessDifferential transcriptional invasion signatures from patient derived organoid models define a functional prognostic tool for head and neck cancer
Clinical outcome for patients suffering from HPV-negative head and neck squamous cell carcinoma (HNSCC) remains poor. This is mostly due to highly invasive tumors that cause loco-regional relapses after initia...
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Article
Open AccessMap** of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth
Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human h...
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Article
Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells
Few cancers can be targeted efficiently by engineered T cell strategies. Here, we show that γδ T cell antigen receptor (γδ TCR)-mediated cancer metabolome targeting can be combined with targeting of cancer-ass...
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Article
Open AccessTemporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity
Pluripotent stem cell (PSC)-derived human brain organoids enable the study of human brain development in vitro. Typically, the fate of PSCs is guided into subsequent specification steps through static medium s...
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Article
Open AccessEngineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis
The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity of human-relevant models for target discovery and compound screening. Here we use human fetal hepatocyte o...
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Article
Open AccessA tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury
Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestin...
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Article
Open AccessOne-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids
Optimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the gen...
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Article
Open AccessDevelopment of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures
Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, u...
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Open AccessAuthor Correction: Transcriptomic profile comparison reveals conservation of ionocytes across multiple organs
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Article
Open AccessHydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures
Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and ...
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Article
Open AccessOrganoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss
Fibrolamellar carcinoma (FLC) is a lethal primary liver cancer, affecting young patients in absence of chronic liver disease. Molecular understanding of FLC tumorigenesis is limited, partly due to the scarcity...
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Article
Open AccessAtypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities
Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or
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Article
Open AccessTranscriptomic profile comparison reveals conservation of ionocytes across multiple organs
Single-cell RNA sequencing has recently led to the identification of a flurry of rare, new cell types, such as the CFTR-high ionocytes in the airway epithelium. Ionocytes appear to be specifically responsible ...
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Article
Open AccessDNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints
Epithelial transdifferentiation is frequent in tissue hyperplasia and contributes to disease in various degrees. Squamous metaplasia (SQM) precedes epidermoid lung cancer, an aggressive and frequent malignancy...
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Article
Open AccessUncovering the mode of action of engineered T cells in patient cancer organoids
Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here w...
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Article
CRISPR engineering in organoids for gene repair and disease modelling
Organoids bridge the gap between 2D cell lines and in vivo studies. With their 3D organization and cellular heterogeneity, adult stem cell-derived organoids closely resemble their tissue of origin. The develop...
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Article
Open AccessIn vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed
With recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming the bottleneck in progressing our ability to model human hepatic tissues in vitro. Here, we introduce ...
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Article
Open AccessRewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors
Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, l...
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Article
Open AccessA bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant
The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human l...
