Snake Venom Gland Organoids

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

doi:10.1016/j.cell.2019.11.038

Cited by 83 publications

(86 citation statements)

References 64 publications

(76 reference statements)

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“…It may be that those peaks displaying the steepest slopes, such as KW1594 peak 22 ( Figure 4 ) are the most likely candidates to be targets of regulatory mechanisms over the course of development. Studies combining transcriptomics and proteomics with novel tools to study gene regulation are forthcoming in snake venomics [ 43 , 44 ] and will shed light on the proportion of venom that is directly regulated vs. impacted in a relative manner by changes in other venom components. More broadly, the presence of ontogenetic shifts in peak abundance that vary from highly linear to highly discrete and sigmoidal in shape suggests that alternate regulatory mechanisms are at play among the genes contributing to the same predatory phenotype of venom.…”

Section: Resultsmentioning

confidence: 99%

Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates

Schonour

Huff

Holding

et al. 2020

Toxins

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Ontogenetic shifts in venom occur in many snakes but establishing their nature as gradual or discrete processes required additional study. We profiled shifts in venom expression from the neonate to adult sizes of two rattlesnake species, the eastern diamondback and the timber rattlesnake. We used serial sampling and venom chromatographic profiling to test if ontogenetic change occurs gradually or discretely. We found evidence for gradual shifts in overall venom composition in six of eight snakes, which sometimes spanned more than two years. Most chromatographic peaks shift gradually, but one quarter shift in a discrete fashion. Analysis of published diet data showed gradual shifts in overall diet composition across the range of body sizes attained by our eight study animals, while the shifts in abundance of different prey classes varied in form from gradual to discrete. Testosterone concentrations were correlated with the change in venom protein composition, but the relationship is not strong enough to suggest causation. Venom research employing simple juvenile versus adult size thresholds may be failing to account for continuous variation in venom composition lifespan. Our results imply that venom shifts represent adaptive matches to dietary shifts and highlight venom for studies of alternative gene regulatory mechanisms.

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Section: Resultsmentioning

confidence: 99%

Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates

Schonour

Huff

Holding

et al. 2020

Toxins

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“…2 and Table 1). Organoid derivation from other domesticated and laboratory animals, including pigs, dogs, cats and rats, have also been described 24,[37][38][39] , and a similar culture setting further allowed an organoid expansion of snake venom glands 40 , underscoring the cross-species versatility of the organoid culture system. It should be noted that the growth factor combinations are not only tailored to individual tissues but also include unique molecules in some cases, such as gastrin for digestive tissues, neuregulin-1 for mammary organoids 7,18,19 , dihydrotestosterone for prostate organoidsd 6,41 and forskolin for human liver bile duct organoids 25 but not for hepatocyte organoids 26 .…”

Section: Somatic Cell-derived Organoids As Prototypes Of Human Epithementioning

confidence: 90%

Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases

2020

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“…In kidney organoids and prostate organogenesis, Wnt activity is critical early-on to promote progenitor outgrowth but then decreases to allow for differentiation (Prins and Putz, 2008;Simons et al, 2012;Takasato et al, 2016). Similarly, in snake venom gland organoids, Wnt agonists must be removed to allow for differentiation and secretory function (Post et al, 2020). Consistently, we observed that lineage-committed cells had lower Wnt activity and selective Wnt inhibition by 1,25D was observed in the lineage-committed cells, but not in KRT13+ stem cells, resulting in enhanced epithelial differentiation in the organoids ( Figure 5E).…”

Section: 25d Regulates Dkk3 In Lineage-committed Cellsmentioning

confidence: 99%

Vitamin D Sufficiency Enhances Differentiation of Patient-Derived Prostate Epithelial Organoids

McCray

Pacheco

Baumann

et al. 2020

Preprint

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Vitamin D is an essential steroid hormone that regulates systemic calcium homeostasis and cell fate decisions, including differentiation in many cell types. The prostate gland is hormonally regulated, requiring steroids for proliferation and terminal differentiation of secretory luminal cells. Vitamin D deficiency is associated with higher risk of lethal prostate cancer with an aggressive dedifferentiated pathology, linking vitamin D sufficiency to epithelial differentiation homeostasis. To determine regulation of prostate epithelial differentiation by vitamin D status, patient-derived benign prostate epithelial organoids were maintained in vitamin D deficient (vehicle) or sufficient (10 nM 1,25-dihydroxyvitamin D) conditions and assessed by phenotype and single cell RNA sequencing. Mechanistic validation demonstrated that vitamin D sufficiency promoted organoid growth and accelerated differentiation of lineage-committed cells by inhibiting canonical Wnt activity and Wnt family member DKK3. Wnt dysregulation is a known contributor to aggressive prostate cancer, thus these findings further link vitamin D deficiency to lethal disease.

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Snake Venom Gland Organoids

Abstract: Highlightsd Snake venom gland cells can be cultured as adult-stem-cellbased organoids d Organoids contain proliferating progenitors and various venom-producing cells d Regional and cellular heterogeneity of venom components is maintained in culture

Cited by 83 publications

References 64 publications

Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates

Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates

Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases

Vitamin D Sufficiency Enhances Differentiation of Patient-Derived Prostate Epithelial Organoids

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