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Snake Venom Gland Organoids.
Cell ( IF 45.5 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.cell.2019.11.038
Yorick Post 1 , Jens Puschhof 1 , Joep Beumer 1 , Harald M Kerkkamp 2 , Merijn A G de Bakker 3 , Julien Slagboom 4 , Buys de Barbanson 1 , Nienke R Wevers 5 , Xandor M Spijkers 6 , Thomas Olivier 7 , Taline D Kazandjian 8 , Stuart Ainsworth 8 , Carmen Lopez Iglesias 9 , Willine J van de Wetering 10 , Maria C Heinz 11 , Ravian L van Ineveld 12 , Regina G D M van Kleef 13 , Harry Begthel 1 , Jeroen Korving 1 , Yotam E Bar-Ephraim 1 , Walter Getreuer 14 , Anne C Rios 12 , Remco H S Westerink 13 , Hugo J G Snippert 11 , Alexander van Oudenaarden 1 , Peter J Peters 9 , Freek J Vonk 15 , Jeroen Kool 16 , Michael K Richardson 3 , Nicholas R Casewell 8 , Hans Clevers 17
Affiliation  

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.

中文翻译:

蛇毒腺有机体。

Wnt依赖性和Lgr5表达定义了多种哺乳动物上皮干细胞类型。在确定的生长因子条件下,此类成体干细胞(ASC)以3D类器官的形式生长,从而概括了相关上皮细胞的基本特征。在这里,我们从几种蛇种建立了长期扩展的毒腺类器官。新组装的海角珊瑚蛇转录组显示类器官表达高水平的毒素转录本。对类器官和原发组织的单细胞RNA测序可鉴定出不同的表达毒液的细胞类型,以及表达已知哺乳动物干细胞标记物同源物的增殖细胞。在类器官培养物中维持了个别毒液成分表达中的硬连线区域异质性。收获的毒液肽反​​映了粗毒液成分并显示出生物学活性。这项研究将类器官技术扩展到爬虫类组织,并描述了代表蛇毒腺的实验性易处理模型系统。
更新日期:2020-01-23
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