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A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development

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A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. / Helker, Christian S. M.; Mullapudi, Sri-teja; Mueller, Laura M.; Preussner, Jens; Tunaru, Sorin; Skog, Oskar; Kwon, Hyouk-bum; Kreuder, Florian; Lancman, Joseph J.; Bonnavion, Remy; Dong, P. Duc Si; Looso, Mario; Offermanns, Stefan; Korsgren, Ole; Spagnoli, Francesca M.; Stainier, Didier Y. R.

In: Development (Cambridge): for advances in developmental biology and stem cells, Vol. 146, No. 14, dev172569, 01.07.2019, p. dev.172569.

Research output: Contribution to journalArticle

Harvard

Helker, CSM, Mullapudi, S, Mueller, LM, Preussner, J, Tunaru, S, Skog, O, Kwon, H, Kreuder, F, Lancman, JJ, Bonnavion, R, Dong, PDS, Looso, M, Offermanns, S, Korsgren, O, Spagnoli, FM & Stainier, DYR 2019, 'A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development', Development (Cambridge): for advances in developmental biology and stem cells, vol. 146, no. 14, dev172569, pp. dev.172569. https://doi.org/10.1242/dev.172569

APA

Helker, C. S. M., Mullapudi, S., Mueller, L. M., Preussner, J., Tunaru, S., Skog, O., Kwon, H., Kreuder, F., Lancman, J. J., Bonnavion, R., Dong, P. D. S., Looso, M., Offermanns, S., Korsgren, O., Spagnoli, F. M., & Stainier, D. Y. R. (2019). A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. Development (Cambridge): for advances in developmental biology and stem cells, 146(14), dev.172569. [dev172569]. https://doi.org/10.1242/dev.172569

Vancouver

Helker CSM, Mullapudi S, Mueller LM, Preussner J, Tunaru S, Skog O et al. A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. Development (Cambridge): for advances in developmental biology and stem cells. 2019 Jul 1;146(14):dev.172569. dev172569. https://doi.org/10.1242/dev.172569

Author

Helker, Christian S. M. ; Mullapudi, Sri-teja ; Mueller, Laura M. ; Preussner, Jens ; Tunaru, Sorin ; Skog, Oskar ; Kwon, Hyouk-bum ; Kreuder, Florian ; Lancman, Joseph J. ; Bonnavion, Remy ; Dong, P. Duc Si ; Looso, Mario ; Offermanns, Stefan ; Korsgren, Ole ; Spagnoli, Francesca M. ; Stainier, Didier Y. R. / A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. In: Development (Cambridge): for advances in developmental biology and stem cells. 2019 ; Vol. 146, No. 14. pp. dev.172569.

Bibtex Download

@article{dc70516cbc2e44d09156b74fc80d2212,
title = "A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development",
abstract = "An early step in pancreas development is marked by the expression of the Pdx1 transcription factor within the pancreatic endoderm where it is required for the specification of all endocrine cell types. Subsequently, Pdx1 expression becomes restricted to the β-cell lineage where it plays a central role in β-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic β-cell differentiation and increase β-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8,000 small molecules for modulators of pdx1 expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Valproic acid (VPA), a HDAC inhibitor, induces pancreatic endoderm formation, while inhibition of TGF-β signaling leads to the transdifferentiation of α-cells to β-cells. HC Toxin, another HDAC inhibitor, enhances β-cell function in primary mouse and human islets. Thus, using a whole-organism screening strategy, this study identified new pdx1 expression modulators which can be used to influence different steps in pancreas and β-cell development.",
keywords = "Pdx1, Small molecule screen, Transdifferentiation, α-Cells, β-Cells",
author = "Helker, {Christian S. M.} and Sri-teja Mullapudi and Mueller, {Laura M.} and Jens Preussner and Sorin Tunaru and Oskar Skog and Hyouk-bum Kwon and Florian Kreuder and Lancman, {Joseph J.} and Remy Bonnavion and Dong, {P. Duc Si} and Mario Looso and Stefan Offermanns and Ole Korsgren and Spagnoli, {Francesca M.} and Stainier, {Didier Y. R.}",
year = "2019",
month = jul,
day = "1",
doi = "10.1242/dev.172569",
language = "English",
volume = "146",
pages = "dev.172569",
journal = "Development (Cambridge): for advances in developmental biology and stem cells",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "14",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development

AU - Helker, Christian S. M.

AU - Mullapudi, Sri-teja

AU - Mueller, Laura M.

AU - Preussner, Jens

AU - Tunaru, Sorin

AU - Skog, Oskar

AU - Kwon, Hyouk-bum

AU - Kreuder, Florian

AU - Lancman, Joseph J.

AU - Bonnavion, Remy

AU - Dong, P. Duc Si

AU - Looso, Mario

AU - Offermanns, Stefan

AU - Korsgren, Ole

AU - Spagnoli, Francesca M.

AU - Stainier, Didier Y. R.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - An early step in pancreas development is marked by the expression of the Pdx1 transcription factor within the pancreatic endoderm where it is required for the specification of all endocrine cell types. Subsequently, Pdx1 expression becomes restricted to the β-cell lineage where it plays a central role in β-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic β-cell differentiation and increase β-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8,000 small molecules for modulators of pdx1 expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Valproic acid (VPA), a HDAC inhibitor, induces pancreatic endoderm formation, while inhibition of TGF-β signaling leads to the transdifferentiation of α-cells to β-cells. HC Toxin, another HDAC inhibitor, enhances β-cell function in primary mouse and human islets. Thus, using a whole-organism screening strategy, this study identified new pdx1 expression modulators which can be used to influence different steps in pancreas and β-cell development.

AB - An early step in pancreas development is marked by the expression of the Pdx1 transcription factor within the pancreatic endoderm where it is required for the specification of all endocrine cell types. Subsequently, Pdx1 expression becomes restricted to the β-cell lineage where it plays a central role in β-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic β-cell differentiation and increase β-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8,000 small molecules for modulators of pdx1 expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Valproic acid (VPA), a HDAC inhibitor, induces pancreatic endoderm formation, while inhibition of TGF-β signaling leads to the transdifferentiation of α-cells to β-cells. HC Toxin, another HDAC inhibitor, enhances β-cell function in primary mouse and human islets. Thus, using a whole-organism screening strategy, this study identified new pdx1 expression modulators which can be used to influence different steps in pancreas and β-cell development.

KW - Pdx1

KW - Small molecule screen

KW - Transdifferentiation

KW - α-Cells

KW - β-Cells

UR - http://www.scopus.com/inward/record.url?scp=85070875087&partnerID=8YFLogxK

U2 - 10.1242/dev.172569

DO - 10.1242/dev.172569

M3 - Article

VL - 146

SP - dev.172569

JO - Development (Cambridge): for advances in developmental biology and stem cells

JF - Development (Cambridge): for advances in developmental biology and stem cells

SN - 0950-1991

IS - 14

M1 - dev172569

ER -

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