Snake Venom Gland Organoids

Yorick Post¹, Jens Puschhof¹, Joep Beumer¹, Harald M Kerkkamp², Merijn A G de Bakker³, Julien Slagboom⁴, Buys de Barbanson¹, Nienke R Wevers⁵, Xandor M Spijkers⁶, Thomas Olivier⁷, Taline D Kazandjian⁸, Stuart Ainsworth⁸, Carmen Lopez Iglesias⁹, Willine J van de Wetering¹⁰, Maria C Heinz¹¹, Ravian L van Ineveld¹², Regina G D M van Kleef¹³, Harry Begthel¹, Jeroen Korving¹, Yotam E Bar-Ephraim¹, Walter Getreuer¹⁴, Anne C Rios¹², Remco H S Westerink¹³, Hugo J G Snippert¹¹, Alexander van Oudenaarden¹, Peter J Peters⁹, Freek J Vonk¹⁵, Jeroen Kool¹⁶, Michael K Richardson³, Nicholas R Casewell⁸, Hans Clevers¹⁷

Affiliations

¹ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands.
² Naturalis Biodiversity Center, 2333 CR Leiden, the Netherlands; Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.
³ Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.
⁴ Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, the Netherlands.
⁵ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands; Department of Cell and Chemical Biology, Leiden University Medical Centre, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
⁶ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands; Department of Translational Neuroscience, Utrecht University Medical Center, 3584 CG Utrecht, the Netherlands.
⁷ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands.
⁸ Centre for Snakebite Research & Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
⁹ The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, the Netherlands.
¹⁰ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, the Netherlands.
¹¹ Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
¹² Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; The Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands.
¹³ Neurotoxicology Research Group, Division of Toxicology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, 3584 CL Utrecht, the Netherlands.
¹⁴ Serpo, 2288 ED Rijswijk, the Netherlands.
¹⁵ Naturalis Biodiversity Center, 2333 CR Leiden, the Netherlands.
¹⁶ Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, the Netherlands; Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute for Molecules Medicines and Systems, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands.
¹⁷ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; The Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.

PMID: 31978343
DOI: 10.1016/j.cell.2019.11.038

Free article

Snake Venom Gland Organoids

Yorick Post et al. Cell. 2020.

Free article

. 2020 Jan 23;180(2):233-247.e21.

doi: 10.1016/j.cell.2019.11.038.

Authors

Affiliations

¹ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands.
² Naturalis Biodiversity Center, 2333 CR Leiden, the Netherlands; Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.
³ Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.
⁴ Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, the Netherlands.
⁵ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands; Department of Cell and Chemical Biology, Leiden University Medical Centre, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
⁶ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands; Department of Translational Neuroscience, Utrecht University Medical Center, 3584 CG Utrecht, the Netherlands.
⁷ Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands.
⁸ Centre for Snakebite Research & Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
⁹ The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, the Netherlands.
¹⁰ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, the Netherlands.
¹¹ Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
¹² Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; The Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands.
¹³ Neurotoxicology Research Group, Division of Toxicology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, 3584 CL Utrecht, the Netherlands.
¹⁴ Serpo, 2288 ED Rijswijk, the Netherlands.
¹⁵ Naturalis Biodiversity Center, 2333 CR Leiden, the Netherlands.
¹⁶ Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, the Netherlands; Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute for Molecules Medicines and Systems, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands.
¹⁷ Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; The Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.

PMID: 31978343
DOI: 10.1016/j.cell.2019.11.038

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.

Keywords: Lgr5; heterogeneity; knock-in reporter; organoid; single cell RNA sequencing; snake; stem cells; transcriptomics; venom gland.

PubMed Disclaimer

Comment in

Omics and organoids - a route to improved anti-venom.
Clyde D. Clyde D. Nat Rev Genet. 2020 Mar;21(3):133. doi: 10.1038/s41576-020-0214-3. Nat Rev Genet. 2020. PMID: 31992867 No abstract available.
Venomous organoids.
Vogt N. Vogt N. Nat Methods. 2020 Apr;17(4):360. doi: 10.1038/s41592-020-0806-z. Nat Methods. 2020. PMID: 32242154 No abstract available.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

200517/Z/16/Z/Wellcome Trust/United Kingdom

LinkOut - more resources

Full Text Sources
- Elsevier Science
Other Literature Sources
- H1 Connect - Access expert opinions and insights on biomedical research.
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Snake Venom Gland Organoids

Affiliations

Snake Venom Gland Organoids

Authors

Affiliations

Abstract

Comment in

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases