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Animal Models

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Division of Comparative Medicine

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Integrin αvβ3 Upregulation in Response to Nutrient Stress Promotes Lung Cancer Cell Metabolic Plasticity

Nam, Cancer Research. 2024.

https://pubmed.ncbi.nlm.nih.gov/38588407/

Tumor-initiating cells can survive in harsh environments via stress tolerance and metabolic flexibility; studies on this topic can yield new targets for cancer therapy. Using cultured cells and live human surgical biopsies of non-small cell lung cancer, researchers demonstrated that nutrient stress drives a metabolic reprogramming cascade that allows tumor cells to thrive despite a nutrient-limiting environment. This cascade results from upregulation of integrin αvβ3, a cancer stem cell marker. In mice, pharmacological or genetic targeting prevented lung cancer cells from evading the effects of nutrient stress, thus blocking tumor initiation. This work suggests that this molecular pathway leads to cancer stem cell reprogramming and could be linked to metabolic flexibility and tumor initiation. Supported by ORIP (K01OD030513), NCI, NIGMS, and NINDS.

DAZL Knockout Pigs as Recipients for Spermatogonial Stem Cell Transplantation

Lara et al., Cells. 2023.

https://pubmed.ncbi.nlm.nih.gov/37947660/

Spermatogonial stem cell (SSC) transplantation is a technique that holds potential for addressing male infertility, as well as generation of genetically modified animal models. DAZL (Deleted in Azoospermia–Like) is a conserved RNA-binding protein important for germ cell development, and DAZL knockout (KO) causes defects in germ cell commitment and differentiation. Investigators characterized DAZL-KO pigs as SSC transplantation recipients. DAZL-KO pigs support donor-derived spermatogenesis following SSC transplantation, but low spermatogenic efficiency currently limits their use for the production of offspring. Supported by ORIP (R01OD016575) and NIGMS.

Increased Collective Migration Correlates With Germline Stem Cell Competition in a Basal Chordate

Fentress and De Tomaso et al., PLOS One. 2023.

https://pubmed.ncbi.nlm.nih.gov/37903140/

Cell competition is a process that compares the relative fitness of progenitor cells and results in healthier cells, contributing a higher proportion to the final tissue composition. Investigators are studying cell competition in a novel model organism, the colonial ascidian, Botryllus schlosseri. They demonstrated that winner germline stem cells show enhanced migratory ability to chemotactic cues ex vivo and that enhanced migration correlates with both expression of the Notch ligand, Jagged, and cluster size. The ability to study conserved aspects of cell migration makes Botryllus an excellent model for future studies on competition, chemotaxis, and collective cell migration. Supported by ORIP (R21OD030520) and NIGMS.

HDAC Inhibitor Titration of Transcription and Axolotl Tail Regeneration

Voss et al., Frontiers in Cell and Development Biology. 2021.

https://pubmed.ncbi.nlm.nih.gov/35036404/

New patterns of gene expression are enacted and regulated during tissue regeneration. Romidepsin, an FDA-approved HDAC inhibitor, potently blocks axolotl embryo tail regeneration by altering initial transcriptional responses to injury. Regeneration inhibitory concentrations of romidepsin increased and decreased the expression of key genes. Single-nuclei RNA sequencing at 6 HPA illustrated that key genes were altered by romidepsin in the same direction across multiple cell types. These results implicate HDAC activity as a transcriptional mechanism that operates across cell types to regulate the alternative expression of genes that associate with regenerative success versus failure outcomes. Supported by ORIP (P40OD019794, R24OD010435, R24OD021479), NICHD, and NIGMS.