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Cell. 2020 Jan 23;180(2):233-247.e21. doi: 10.1016/j.cell.2019.11.038.

Snake Venom Gland Organoids.

Author information

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.

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

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

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