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-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 › Article › peer-review

75 Citations (Scopus)

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

Keywords

heterogeneity
knock-in reporter
Lgr5
organoid
single cell RNA sequencing
snake
stem cells
transcriptomics
venom gland

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10.1016/j.cell.2019.11.038

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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.e21. https://doi.org/10.1016/j.cell.2019.11.038

@article{5e7c9669ce734acfad540d105751bb5e,

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.",

keywords = "heterogeneity, knock-in reporter, Lgr5, organoid, single cell RNA sequencing, snake, stem cells, transcriptomics, 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",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = jan,

day = "23",

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

language = "English",

volume = "180",

pages = "233--247.e21",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "2",

}

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, pp. 233-247.e21. 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.

KW - heterogeneity

KW - knock-in reporter

KW - Lgr5

KW - organoid

KW - single cell RNA sequencing

KW - snake

KW - stem cells

KW - transcriptomics

KW - venom gland

UR - http://www.scopus.com/inward/record.url?scp=85077840511&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.11.038

DO - 10.1016/j.cell.2019.11.038

M3 - Article

C2 - 31978343

AN - SCOPUS:85077840511

SN - 0092-8674

VL - 180

SP - 233-247.e21

JO - Cell

JF - Cell

IS - 2

ER -

Snake Venom Gland Organoids

Abstract

Keywords

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