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-Ephraim; Walter 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

doi:10.1016/j.cell.2019.11.038

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-Ephraim

Walter 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

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.
Naturalis Biodiversity Center, 2333 CR Leiden, the Netherlands; Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.
Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, 1081 LA Amsterdam, the Netherlands.
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.
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.
Mimetas BV, Organ-on-a-Chip Company, 2333 CH Leiden, the Netherlands.
Centre for Snakebite Research & Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, the Netherlands.
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.
Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands; The Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands.
Serpo, 2288 ED Rijswijk, the Netherlands.
Institute of Biology Leiden, Department of Animal Science and Health, 2333 BE Leiden, the Netherlands.

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	e21
Pages (from-to)	233-247
Number of pages	37
Journal	Cell
Volume	180
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2019.11.038
Publication status	Published - 23 Jan 2020

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10.1016/j.cell.2019.11.038

Snake Venom Gland OrganoidsFinal published version, 10.5 MBLicence: Taverne

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Post, Y., Puschhof, J., Beumer, J., Kerkkamp, H. M., de Bakker, M. A. G., Slagboom, J., de Barbanson, B., Wevers, N. R., Spijkers, X. M., Olivier, T., Kazandjian, T. D., Ainsworth, S., Iglesias, C. L., van de Wetering, W. J., Heinz, M. C., van Ineveld, R. L., van Kleef, R. G. D. M., Begthel, H., Korving, J., ... Clevers, H. (2020). Snake Venom Gland Organoids. Cell, 180(2), 233-247. Article e21. https://doi.org/10.1016/j.cell.2019.11.038

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title = "Snake Venom Gland Organoids",

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.",

author = "Yorick Post and Jens Puschhof and Joep Beumer and Kerkkamp, \{Harald M\} and \{de Bakker\}, \{Merijn A G\} and Julien Slagboom and \{de Barbanson\}, Buys and Wevers, \{Nienke R\} and Spijkers, \{Xandor M\} and Thomas Olivier and Kazandjian, \{Taline D\} and Stuart Ainsworth and Iglesias, \{Carmen Lopez\} and \{van de Wetering\}, \{Willine J\} and Heinz, \{Maria C\} and \{van Ineveld\}, \{Ravian L\} and \{van Kleef\}, \{Regina G D M\} and Harry Begthel and Jeroen Korving and Bar-Ephraim, \{Yotam E\} and Walter Getreuer and Rios, \{Anne C\} and Westerink, \{Remco H S\} and Snippert, \{Hugo J G\} and \{van Oudenaarden\}, Alexander and Peters, \{Peter J\} and Vonk, \{Freek J\} and Jeroen Kool and Richardson, \{Michael K\} and Casewell, \{Nicholas R\} and Hans Clevers",

year = "2020",

month = jan,

day = "23",

doi = "10.1016/j.cell.2019.11.038",

language = "English",

volume = "180",

pages = "233--247",

journal = "Cell",

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Post, Y, Puschhof, J, Beumer, J, Kerkkamp, HM, de Bakker, MAG, Slagboom, J, de Barbanson, B, Wevers, NR, Spijkers, XM, Olivier, T, Kazandjian, TD, Ainsworth, S, Iglesias, CL, van de Wetering, WJ, Heinz, MC, van Ineveld, RL, van Kleef, RGDM, Begthel, H, Korving, J, Bar-Ephraim, YE, Getreuer, W, Rios, AC, Westerink, RHS, Snippert, HJG, van Oudenaarden, A, Peters, PJ, Vonk, FJ, Kool, J, Richardson, MK, Casewell, NR & Clevers, H 2020, 'Snake Venom Gland Organoids', Cell, vol. 180, no. 2, e21, pp. 233-247. https://doi.org/10.1016/j.cell.2019.11.038

TY - JOUR

T1 - Snake Venom Gland Organoids

AU - Post, Yorick

AU - Puschhof, Jens

AU - Beumer, Joep

AU - Kerkkamp, Harald M

AU - de Bakker, Merijn A G

AU - Slagboom, Julien

AU - de Barbanson, Buys

AU - Wevers, Nienke R

AU - Spijkers, Xandor M

AU - Olivier, Thomas

AU - Kazandjian, Taline D

AU - Ainsworth, Stuart

AU - Iglesias, Carmen Lopez

AU - van de Wetering, Willine J

AU - Heinz, Maria C

AU - van Ineveld, Ravian L

AU - van Kleef, Regina G D M

AU - Begthel, Harry

AU - Korving, Jeroen

AU - Bar-Ephraim, Yotam E

AU - Getreuer, Walter

AU - Rios, Anne C

AU - Westerink, Remco H S

AU - Snippert, Hugo J G

AU - van Oudenaarden, Alexander

AU - Peters, Peter J

AU - Vonk, Freek J

AU - Kool, Jeroen

AU - Richardson, Michael K

AU - Casewell, Nicholas R

AU - Clevers, Hans

PY - 2020/1/23

Y1 - 2020/1/23

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2019.11.038

DO - 10.1016/j.cell.2019.11.038

M3 - Article

C2 - 31978343

SN - 0092-8674

VL - 180

SP - 233

EP - 247

JO - Cell

JF - Cell

IS - 2

M1 - e21

ER -

Snake Venom Gland Organoids

Abstract

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