Appearance
Snake Venom Gland Organoids.
Literature Information
| DOI | 10.1016/j.cell.2019.11.038 |
|---|---|
| PMID | 31978343 |
| Journal | Cell |
| Impact Factor | 42.5 |
| JCR Quartile | Q1 |
| Publication Year | 2020 |
| Times Cited | 56 |
| Keywords | Lgr5, heterogeneity, knock-in reporter, organoid, single cell RNA sequencing |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't |
| ISSN | 0092-8674 |
| Pages | 233-247.e21 |
| Issue | 180(2) |
| Authors | Yorick Post, Jens Puschhof, Joep Beumer, Harald M Kerkkamp, Merijn A G de Bakker, Julien Slagboom, Buys de Barbanson, Nienke R Wevers, Xandor M Spijkers, Thomas Olivier, Taline D Kazandjian, Stuart Ainsworth, Carmen Lopez Iglesias, Willine J van de Wetering, Maria C Heinz, Ravian L van Ineveld, Regina G D M van Kleef, Harry Begthel, Jeroen Korving, Yotam E Bar-Ephraim, Walter Getreuer, Anne C Rios, Remco H S Westerink, Hugo J G Snippert, Alexander van Oudenaarden, Peter J Peters, Freek J Vonk, Jeroen Kool, Michael K Richardson, Nicholas R Casewell, Hans Clevers |
TL;DR
This study establishes long-term expanding organoids from snake venom glands, revealing that these organoids maintain high levels of toxin transcripts and distinct venom-expressing cell types, along with mammalian stem cell marker homologs. By demonstrating that organoid technology can be applied to reptilian tissues, this research provides a novel model system for studying snake venom biology and its components.
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Lgr5 · heterogeneity · knock-in reporter · organoid · single cell RNA sequencing
Abstract
Wnt dependency and Lgr5 expression define multiple mammalian epithelial stem cell types. Under defined growth factor conditions, such adult stem cells (ASCs) grow as 3D organoids that recapitulate essential features of the pertinent epithelium. Here, we establish long-term expanding venom gland organoids from several snake species. The newly assembled transcriptome of the Cape coral snake reveals that organoids express high levels of toxin transcripts. Single-cell RNA sequencing of both organoids and primary tissue identifies distinct venom-expressing cell types as well as proliferative cells expressing homologs of known mammalian stem cell markers. A hard-wired regional heterogeneity in the expression of individual venom components is maintained in organoid cultures. Harvested venom peptides reflect crude venom composition and display biological activity. This study extends organoid technology to reptilian tissues and describes an experimentally tractable model system representing the snake venom gland.
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Primary Questions Addressed
- What are the implications of using snake venom gland organoids for studying venom composition and function?
- How do the growth factor conditions affect the differentiation of snake venom gland organoids compared to other epithelial organoids?
- In what ways could the findings from snake venom gland organoids contribute to the development of new therapeutic agents or antivenoms?
- What specific challenges might researchers face when establishing and maintaining organoids from different snake species?
- How does the regional heterogeneity in venom component expression within organoids compare to that observed in vivo in snake venom glands?
Key Findings
Key Insights
Research Background and Objectives: The study is centered around the exploration of adult stem cells (ASCs) and their ability to form three-dimensional (3D) organoids that mimic the architecture and function of specific epithelial tissues. While much work has been done with mammalian ASCs, there is a gap in understanding stem cell behaviors in non-mammalian species, particularly reptiles. The primary objective of this research was to establish long-term expanding organoids from snake venom glands, providing insights into venom production and the biology of reptilian epithelial stem cells.
Main Methods and Findings: The researchers developed organoids from the venom glands of several snake species, focusing on the Cape coral snake. They conducted transcriptomic analyses to assemble a comprehensive gene expression profile of the organoids, revealing a high expression of toxin-related transcripts. Utilizing single-cell RNA sequencing, they identified distinct venom-expressing cell types within the organoids and the primary tissue, as well as proliferative cells that expressed homologs of mammalian stem cell markers. Notably, the organoids maintained a spatial heterogeneity in the expression of individual venom components, reflecting the natural regional variations found in vivo. The harvested venom peptides from these organoids not only mirrored the composition of crude venom but also exhibited biological activity, indicating that the organoids can produce functional venom components.
Core Conclusions: This study successfully extends organoid technology to reptilian tissues, demonstrating that snake venom glands can be modeled in vitro through organoid cultures. The findings highlight the potential of these organoids to serve as a valuable experimental platform for studying the biology of venom production and the underlying mechanisms of venom-associated pathophysiology. The ability to generate and analyze venom components from these organoids opens up new avenues for research in toxinology and regenerative medicine.
Research Significance and Impact: The establishment of venom gland organoids represents a significant advancement in the field of organoid research, particularly for non-mammalian species. This model system not only facilitates a deeper understanding of the evolutionary adaptations of reptilian venom but also provides a unique opportunity to investigate the regenerative properties of reptilian stem cells. Furthermore, the findings could have broader implications for the development of novel therapeutic agents derived from snake venoms, enhancing our understanding of toxin interactions and their potential applications in medicine. Overall, this research contributes to a more comprehensive understanding of the biology of reptiles and the functional roles of their venoms, paving the way for future studies in evolutionary biology, pharmacology, and regenerative medicine.
Literatures Citing This Work
- A brief history of organoids. - Claudia Corrò;Laura Novellasdemunt;Vivian S W Li - American journal of physiology. Cell physiology (2020)
- Toxinology provides multidirectional and multidimensional opportunities: A personal perspective. - R Manjunatha Kini - Toxicon: X (2020)
- Causes and Consequences of Snake Venom Variation. - Nicholas R Casewell;Timothy N W Jackson;Andreas H Laustsen;Kartik Sunagar - Trends in pharmacological sciences (2020)
- Translating Embryogenesis to Generate Organoids: Novel Approaches to Personalized Medicine. - Sounak Sahu;Shyam K Sharan - iScience (2020)
- Cancer research using organoid technology. - Kai Kretzschmar - Journal of molecular medicine (Berlin, Germany) (2021)
- Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates. - Richard B Schonour;Emma M Huff;Matthew L Holding;Natalie M Claunch;Schyler A Ellsworth;Michael P Hogan;Kenneth Wray;James McGivern;Mark J Margres;Timothy J Colston;Darin R Rokyta - Toxins (2020)
- Physiological demands and signaling associated with snake venom production and storage illustrated by transcriptional analyses of venom glands. - Blair W Perry;Drew R Schield;Aundrea K Westfall;Stephen P Mackessy;Todd A Castoe - Scientific reports (2020)
- Organoids to model liver disease. - Sandro Nuciforo;Markus H Heim - JHEP reports : innovation in hepatology (2021)
- Insights into how development and life-history dynamics shape the evolution of venom. - Joachim M Surm;Yehu Moran - EvoDevo (2021)
- Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids. - Tara McCray;Julian V Pacheco;Candice C Loitz;Jason Garcia;Bethany Baumann;Michael J Schlicht;Klara Valyi-Nagy;Michael R Abern;Larisa Nonn - iScience (2021)
... (46 more literatures)
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