Snake Venom Gland Organoids

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-EphraimWalter 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

Research output: Contribution to journal/periodicalArticleScientificpeer-review


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.

Original languageEnglish
Pages (from-to)233-247.e21
Issue number2
Publication statusPublished - 23 Jan 2020


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