| Literature DB >> 31978343 |
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.
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.Entities:
Keywords: Lgr5; heterogeneity; knock-in reporter; organoid; single cell RNA sequencing; snake; stem cells; transcriptomics; venom gland
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Year: 2020 PMID： 31978343 DOI： 10.1016/j.cell.2019.11.038
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582