Biology subjects

Samuelson, L. C.

Publications and source records attributed to Samuelson, L. C..

3 recordsLinked to original sources

bioRxiv2026

Paneth cell-derived Notch ligands DLL1 and DLL4 are crucial for intestinal crypt base stem cells.

Notch signaling is essential for maintaining intestinal stem cell activity and directing epithelial cell fate. Paneth cells have been proposed to be niche cells, providing Notch signal to neighboring stem cells through expression of the key Notch ligands DLL1 and DLL4. However, intestinal stem cells persist in the absence of Paneth cells. Here, we used genetic mouse models to clarify the role of Paneth cell-derived Notch ligands for stem cell function. Paneth cell-specific deletion of Dll1 and Dll4 resulted in loss of crypt base stem cells, with no effect on overall crypt cell proliferation. Organoid growth was reduced in knockout mice, suggesting reduced stem cell function. Upon irradiation injury, stem cell return and crypt regeneration were significantly impaired in the Notch ligand-deleted mice. These findings suggest that Paneth cell-derived Notch ligands DLL1 and DLL4 are crucial for crypt base stem cell maintenance and for crypt regeneration after injury.

cell biology↗

bioRxiv2025

Nuclei sense complex tissue shape and direct intestinal stem cell fate

Tissue architecture and function are influenced by mechanical cues. Yet, how cell nuclei sense forces within 3D tissues and dictate differentiation remains unknown as prior studies focused on isolated mesenchymal cells, which fail to fully predict tissue-level mechanical properties. We fill this knowledge gap utilizing live reporters and material-based organoid models. We posit the nucleus as an active mechanosensor of tissue shape, with levels of the nuclear scaffolding protein lamin-A varying across intestinal stem cell differentiation trajectory. Elevated forces on differentiated Paneth cell nuclei, in both organoids and tissue explants, increase lamin-A and nuclear wrinkling. Enhancing nuclear mechanotransduction primes cell differentiation, in otherwise stem promoting conditions, revealing that nuclear mechanics can direct stem cell fate. By engineering spatiotemporally controlled de novo tissue curvature with photo-degradable hydrogels, we direct spatially patterned lamin-A levels across mouse and human organoids of healthy and diseased origin, uncovering conserved nuclear mechanosensing pathway in epithelial tissues.

bioengineering↗

bioRxiv2017

Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells

The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from 4 adenoma organoid lines and were subjected to RNA-sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA-seq data from adenoma and normal organoids, we found correlations between LGR5 and CRC- specific genes, including DKK4 (dickkopf WNT signaling pathway inhibitor 4) and SMOC2 (SPARC related modular calcium binding 2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.

cancer biology↗