Selected Grantee Publications
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- 6 results found
- Aquatic Vertebrate Models
- Immunology
- Stem Cells/Regenerative Medicine
Differentiation Success of Reprogrammed Cells Is Heterogeneous In Vivo and Modulated by Somatic Cell Identity Memory
Zikmund et al., Stem Cell Reports. 2025.
https://pubmed.ncbi.nlm.nih.gov/40086446
Nuclear reprogramming can change cellular fates, yet reprogramming efficiency is low, and the resulting cell types are often not functional. Researchers used nuclear transfer to Xenopus eggs to follow single cells during reprogramming in vivo. Results showed that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. Subsets of reprogramming-resistant cells fail to form functional cell types and undergo cell death or disrupt normal body patterning. Reducing expression levels of genes specific to the cell type of origin leads to better reprogramming and improved differentiation trajectories. This study demonstrates that failing to reprogram in vivo is cell type specific and emphasizes the necessity of minimizing aberrant transcripts of the previous somatic identity for improving reprogramming. Supported by ORIP (R24OD031956).
Injury-Induced Cooperation of InhibinβA and JunB is Essential for Cell Proliferation in Xenopus Tadpole Tail Regeneration
Nakamura et al., Scientific Reports. 2024.
https://pubmed.ncbi.nlm.nih.gov/38355764/
Certain animal species (e.g., amphibians) that can regenerate lost tissues and limbs after injury offer potential for applications in regenerative medicine. Cell proliferation is essential for the reconstruction of injured tissue, but the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Using Xenopus tropicalis, investigators examined the effects of injury on the expression of inhibin subunit beta A (inhba) and junB proto-oncogene (junb). Their findings shed light on the mechanisms underlying injury-induced cell proliferation in regenerative animals. Supported by ORIP (P40OD010997, R24OD030008).
Production and Characterization of Monoclonal Antibodies to Xenopus Proteins
Horr et al., Development. 2023.
https://pubmed.ncbi.nlm.nih.gov/36789951/
Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, the authors refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, they describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. Supported by ORIP (R24OD021485, S10OD010645) and NIDCR.
Evolution of the Nitric Oxide Synthase Family in Vertebrates and Novel Insights in Gill Development
Annona et al., Proceedings of the Royal Society B. 2022.
https://www.doi.org/10.1098/rspb.2022.0667
Nitric oxide (NO) plays essential roles in biological systems, including cardiovascular homeostasis, neurotransmission, and immunity. Knowledge of NO synthases (NOS) is substantial, but the origin of nos gene orthologues in fishes, with respect to tetrapods, remains largely unknown. The recent identification of nos3 in the spotted gar, considered lost in this lineage, prompted the authors to explore nos gene evolution. Here, they report that nos2 experienced several lineage-specific gene duplications and losses. Additionally, nos3 was found to be lost independently in two teleost lineages, Elopomorpha and Clupeocephala. Further, the expression of at least one nos paralogue in gills of developing shark, bichir, sturgeon, and gar, but not in gills of lamprey, suggests nos expression in the gill might have arisen in the last common ancestor of gnathostomes. These results provide a framework for further research on the role of nos genes. Supported by ORIP (P40OD019794, R01OD011116).
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.
The SARS-CoV-2 Receptor and Other Key Components of the Renin-Angiotensin-Aldosterone System Related to COVID-19 are Expressed in Enterocytes in Larval Zebrafish
Postlethwait et al., Biology Open. 2021.
https://bio.biologists.org/content/10/3/bio058172.article-info
Hypertension and respiratory inflammation are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from dropping blood pressure via Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II and serves as the SARS-CoV-2 receptor. To exploit zebrafish to understand the relationship of RAAS to COVID-19, the group conducted genomic and phylogenetic analyses. Results identified a type of enterocyte as the expression site of zebrafish orthologs of key RAAS components, including the SARS-CoV-2 co-receptor. Results identified vascular cell subtypes expressing Ang II receptors and identified cell types to exploit zebrafish as a model for understanding COVID-19 mechanisms. Supported by ORIP (R24OD026591, R01OD011116), NIGMS, NICHD.