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49 results on '"Middendorp, Sabine"'

2. Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency

Author

van Rijn, Jorik M., Ardy, Rico Chandra, Kuloğlu, Zarife, Härter, Bettina, van Haaften-Visser, Désirée Y., van der Doef, Hubert P.J., van Hoesel, Marliek, Kansu, Aydan, van Vugt, Anke H.M., Thian, Marini, Kokke, Freddy T.M., Krolo, Ana, Başaran, Meryem Keçeli, Kaya, Neslihan Gurcan, Aksu, Aysel Ünlüsoy, Dalgıç, Buket, Ozcay, Figen, Baris, Zeren, Kain, Renate, Stigter, Edwin C.A., Lichtenbelt, Klaske D., Massink, Maarten P.G., Duran, Karen J., Verheij, Joke B.G.M, Lugtenberg, Dorien, Nikkels, Peter G.J., Brouwer, Henricus G.F., Verkade, Henkjan J., Scheenstra, René, Spee, Bart, Nieuwenhuis, Edward E.S., Coffer, Paul J., Janecke, Andreas R., van Haaften, Gijs, Houwen, Roderick H.J., Müller, Thomas, Middendorp, Sabine, and Boztug, Kaan

Published
2018
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3. Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids

Author

CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, van Mil, Saskia W C, CMM Groep Van Mil, Cancer, CMM Groep Burgering, Child Health, Regenerative Medicine and Stem Cells, CMM, de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin, Gulersonmez, M Can, Ramos Pittol, Jose M, Middendorp, Sabine, Takkenberg, R Bart, and van Mil, Saskia W C

Published
2023

5. Issue Cover

Author

de Wit, Koos, primary, Beuers, Ulrich, additional, Mukha, Anna, additional, Stigter, Edwin C. A., additional, Gulersonmez, M. Can, additional, Ramos Pittol, Jose M., additional, Middendorp, Sabine, additional, Takkenberg, R. Bart, additional, and van Mil, Saskia W. C., additional

Published
2023
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7. An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

Author

Schneeberger, Kerstin, Vogel, Georg F., Teunissen, Hans, van Ommen, Domenique D., Begthel, Harry, Bouazzaoui, Layla El, van Vugt, Anke H. M., Beekman, Jeffrey M., Klumperman, Judith, Müller, Thomas, Janecke, Andreas, Gerner, Patrick, Huber, Lukas A., Hess, Michael W., Clevers, Hans, van Es, Johan H., Nieuwenhuis, Edward E. S., and Middendorp, Sabine

Published
2015

8. 215 Targeting ovarian carcinoma with GDT002, a first-in-class γδTCR-based T cell therapy

Author

Drent, Esther, primary, Middendorp, Sabine, additional, Bisso, Andrea, additional, Baardman, Sjoerd, additional, Verweij, Dagmar, additional, Salcedo, Estefania, additional, Coomans, Chris, additional, Braem, Steven, additional, Weg, Sander van de, additional, Meijer, Menno, additional, Proost, Natalie, additional, Ven, Marieke van de, additional, Norell, Haakan, additional, Loenen, Marleen van, additional, Emami, Nia, additional, Melief, Sara, additional, Gobessi, Stefania, additional, and Throsby, Mark, additional

Published
2022
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9. Rifaximin stimulates nitrogen detoxification by PXR‐independent mechanisms in human small intestinal organoids.

Author

de Wit, Koos, Beuers, Ulrich, Mukha, Anna, Stigter, Edwin C. A., Gulersonmez, M. Can, Ramos Pittol, Jose M., Middendorp, Sabine, Takkenberg, R. Bart, and van Mil, Saskia W. C.

Subjects
RIFAXIMIN, PREGNANE X receptor, AMINO acid metabolism, HEPATIC encephalopathy, ORGANOIDS
Abstract

Background and Aims: Recurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear. We used human small intestinal (hSI) organoids to study whether rifaximin, via PXR activation, affects the epithelial biotransformation machinery, and to gain understanding of its low systemic availability. Methods: We generated PXR knockdown hSI organoids via lentiviral delivery of short hairpin RNAs. Organoids were cultured for 24 h with rifaximin or rifampicin. RNA‐sequencing and metabolomics were performed to analyse gene expression and amino acid metabolism. Luminal rifaximin was quantified by photospectrometry. Results: Treatment of wild‐type hSI organoids with rifaximin resulted in >twofold differential expression of 131 genes compared to DMSO. These effects were largely PXR independent and related to amino acid metabolism. Rifaximin decreased expression of glutaminase‐2 and increased expression of asparagine synthetase and solute carrier 7A11, thereby increasing intracellular glutamine and asparagine concentrations, indicating active ammonia detoxification. Rifaximin was apically excreted into the lumen in an ATP binding cassette B1 (ABCB1)‐dependent manner. Conclusions: Rifaximin—after uptake into enterocytes—stimulates intracellular nitrogen detoxification by PXR‐independent mechanisms. Active apical excretion of rifaximin by ABCB1 into the intestinal lumen explains its low systemic bioavailability. Our study implies that rifaximin, next to modulation of the microbiome, has direct effects on ammonia scavenging in the human small intestinal epithelium. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Erratum: DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells

Author

Child Health, MDL onderzoek 2, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, MDL onderzoek 1, Onderzoek, Infection & Immunity, MDL patientenzorg, van Rijn, Jorik M, van Hoesel, Marliek, de Heus, Cecilia, van Vugt, Anke H M, Klumperman, Judith, Nieuwenhuis, Edward E S, Houwen, Roderick H J, Middendorp, Sabine, Child Health, MDL onderzoek 2, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, MDL onderzoek 1, Onderzoek, Infection & Immunity, MDL patientenzorg, van Rijn, Jorik M, van Hoesel, Marliek, de Heus, Cecilia, van Vugt, Anke H M, Klumperman, Judith, Nieuwenhuis, Edward E S, Houwen, Roderick H J, and Middendorp, Sabine

Published
2021

11. A Potential Treatment of Congenital Sodium Diarrhea in Patients With Activating GUCY2C Mutations

Author

MDL patientenzorg, Child Health, Regenerative Medicine and Stem Cells, van Vugt, Anke H M, Bijvelds, Marcel J C, de Jonge, Hugo R, Meijsen, Kelly F, Restin, Tanja, Bryant, Manuel B, Ballauff, Antje, Koot, Bart, Müller, Thomas, Houwen, Roderick H J, Janecke, Andreas R, Middendorp, Sabine, MDL patientenzorg, Child Health, Regenerative Medicine and Stem Cells, van Vugt, Anke H M, Bijvelds, Marcel J C, de Jonge, Hugo R, Meijsen, Kelly F, Restin, Tanja, Bryant, Manuel B, Ballauff, Antje, Koot, Bart, Müller, Thomas, Houwen, Roderick H J, Janecke, Andreas R, and Middendorp, Sabine

Published
2021

12. A Potential Treatment of Congenital Sodium Diarrhea in Patients With Activating GUCY2C Mutations

Author

van Vugt, Anke H M, Bijvelds, Marcel J C, de Jonge, Hugo R, Meijsen, Kelly F, Restin, Tanja, Bryant, Manuel B, Ballauff, Antje, Koot, Bart, Müller, Thomas, Houwen, Roderick H J, Janecke, Andreas R; https://orcid.org/0000-0001-7155-0315, Middendorp, Sabine, van Vugt, Anke H M, Bijvelds, Marcel J C, de Jonge, Hugo R, Meijsen, Kelly F, Restin, Tanja, Bryant, Manuel B, Ballauff, Antje, Koot, Bart, Müller, Thomas, Houwen, Roderick H J, Janecke, Andreas R; https://orcid.org/0000-0001-7155-0315, and Middendorp, Sabine

Abstract

INTRODUCTION Gain-of-function mutations in guanylyl cyclase C (GCC) result in persistent diarrhea with perinatal onset. We investigated a specific GCC inhibitor, SSP2518, for its potential to treat this disorder. METHODS We investigated the effect of SSP2518 on GCC-mediated intracellular cyclic guanosine monophosphate (cGMP) levels and on GCC-mediated chloride secretion in intestinal organoids from 3 patients with distinct activating GCC mutations and from controls, with and without stimulation of GCC with heat-stable enterotoxin. RESULTS Patient-derived organoids had significantly higher basal cGMP levels than control organoids, which were lowered by SSP2518 to levels found in control organoids. In addition, SSP2518 significantly reduced cGMP levels and chloride secretion in patient-derived and control organoids (P < 0.05 for all comparisons) after heat-stable enterotoxin stimulation. DISCUSSION We reported in this study that the GCC inhibitor SSP2518 normalizes cGMP levels in intestinal organoids derived from patients with GCC gain-of-function mutations and markedly reduces cystic fibrosis transmembrane conductance regulator-dependent chloride secretion, the driver of persistent diarrhea.

Published
2021

13. Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy

Author

van Rijn, Jorik M., Werner, Lael, Aydemir, Yusuf, Spronck, Joey M. A., Pode-Shakked, Ben, van Hoesel, Marliek, Shimshoni, Elee, Polak-Charcon, Sylvie, Talmi, Liron, Eren, Makbule, Weiss, Batia, Houwen, Roderick H. J., Barshack, Iris, Somech, Raz, Nieuwenhuis, Edward E. S., Sagi, Irit, Raas-Rothschild, Annick, Middendorp, Sabine, Shouval, Dror S., van Rijn, Jorik M., Werner, Lael, Aydemir, Yusuf, Spronck, Joey M. A., Pode-Shakked, Ben, van Hoesel, Marliek, Shimshoni, Elee, Polak-Charcon, Sylvie, Talmi, Liron, Eren, Makbule, Weiss, Batia, Houwen, Roderick H. J., Barshack, Iris, Somech, Raz, Nieuwenhuis, Edward E. S., Sagi, Irit, Raas-Rothschild, Annick, Middendorp, Sabine, and Shouval, Dror S.

Abstract

Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2(KO) organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE., De två första författarna delar förstaförfattarskapet.

Published
2020
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14. Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy

Author

Child Health, MDL onderzoek 2, MS CGO, MDL patientenzorg, Onderzoek, MDL onderzoek 1, Infection & Immunity, Regenerative Medicine and Stem Cells, van Rijn, Jorik M, Werner, Lael, Aydemir, Yusuf, Spronck, Joey M A, Pode-Shakked, Ben, van Hoesel, Marliek, Shimshoni, Elee, Polak-Charcon, Sylvie, Talmi, Liron, Eren, Makbule, Weiss, Batia, H J Houwen, Roderick, Barshack, Iris, Somech, Raz, Nieuwenhuis, Edward E S, Sagi, Irit, Raas-Rothschild, Annick, Middendorp, Sabine, Shouval, Dror S, Child Health, MDL onderzoek 2, MS CGO, MDL patientenzorg, Onderzoek, MDL onderzoek 1, Infection & Immunity, Regenerative Medicine and Stem Cells, van Rijn, Jorik M, Werner, Lael, Aydemir, Yusuf, Spronck, Joey M A, Pode-Shakked, Ben, van Hoesel, Marliek, Shimshoni, Elee, Polak-Charcon, Sylvie, Talmi, Liron, Eren, Makbule, Weiss, Batia, H J Houwen, Roderick, Barshack, Iris, Somech, Raz, Nieuwenhuis, Edward E S, Sagi, Irit, Raas-Rothschild, Annick, Middendorp, Sabine, and Shouval, Dror S

Published
2020

16. Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy

Author

van Rijn, Jorik M., primary, Werner, Lael, additional, Aydemir, Yusuf, additional, Spronck, Joey M.A., additional, Pode-Shakked, Ben, additional, van Hoesel, Marliek, additional, Shimshoni, Elee, additional, Polak-Charcon, Sylvie, additional, Talmi, Liron, additional, Eren, Makbule, additional, Weiss, Batia, additional, H.J. Houwen, Roderick, additional, Barshack, Iris, additional, Somech, Raz, additional, Nieuwenhuis, Edward E.S., additional, Sagi, Irit, additional, Raas-Rothschild, Annick, additional, Middendorp, Sabine, additional, and Shouval, Dror S., additional

Published
2020
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17. Bipotent Liver Progenitors Depend on Glycolysis and Mitochondrial Pyruvate Oxidation for Stem Cell Functions

Author

Schene, Imre Firmin, primary, Ramos, Rúben J., additional, van Vugt, Anke H.M., additional, Truong, Hoa, additional, van den Heuvel, Dave J., additional, Gerritsen, Hans C., additional, Houtkooper, Riekelt H., additional, van Weeghel, Michel, additional, Middendorp, Sabine, additional, Mokry, Michal, additional, Spee, Bart, additional, Schneeberger, Kerstin, additional, Nikkels, Peter G.J., additional, Huch, Meritxell, additional, Clevers, Hans, additional, Nieuwenhuis, Edward E.S., additional, van Hasselt, Peter M., additional, and Fuchs, Sabine A., additional

Published
2020
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18. Tissue-specific mutation accumulation in human adult stem cells during life

Author

Blokzijl, Francis, de Ligt, Joep, Jager, Myrthe, Sasselli, Valentina, Roerink, Sophie, Sasaki, Nobuo, Huch, Meritxell, Boymans, Sander, Kuijk, Ewart, Prins, Pjotr, Nijman, Isaac J., Martincorena, Inigo, Mokry, Michal, Wiegerinck, Caroline L., Middendorp, Sabine, Sato, Toshiro, Schwank, Gerald, Nieuwenhuis, Edward E. S., Verstegen, Monique M. A., van der Laan, Luc J. W., de Jonge, Jeroen, IJzermans, Jan N. M., Vries, Robert G., van de Wetering, Marc, Stratton, Michael R., Clevers, Hans, Cuppen, Edwin, and van Boxtel, Ruben

Subjects
Gene mutation -- Observations, Stem cells -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Francis Blokzijl [1, 2]; Joep de Ligt [1, 2]; Myrthe Jager [1, 2]; Valentina Sasselli [2]; Sophie Roerink [3]; Nobuo Sasaki [2]; Meritxell Huch [2]; Sander Boymans [1, 2]; [...]

Published
2016
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19. A Fluorescence-based Assay for Characterization and Quantification of Lipid Droplet Formation in Human Intestinal Organoids

Author

van Rijn, Jorik M., van Hoesel, Marliek, Middendorp, Sabine, van Rijn, Jorik M., van Hoesel, Marliek, and Middendorp, Sabine

Abstract

Dietary lipids are taken up as free fatty acids (FAs) by the intestinal epithelium. These FAs are intracellularly converted into triglyceride (TG) molecules, before they are packaged into chylomicrons for transport to the lymph or into cytosolic lipid droplets (LDs) for intracellular storage. A crucial step for the formation of LDs is the catalytic activity of diacylglycerol acyltransferases (DGAT) in the final step of TG synthesis. LDs are important to buffer toxic lipid species and regulate cellular metabolism in different cell types. Since the human intestinal epithelium is regularly confronted with high concentrations of lipids, LD formation is of great importance to regulate homeostasis. Here we describe a simple assay for the characterization and quantification of LD formation (LDF) upon stimulation with the most common unsaturated fatty acid, oleic acid, in human intestinal organoids. The LDF assay is based on the LD-specific fluorescent dye LD540, which allows for quantification of LDs by confocal microscopy, fluorescent plate reader, or flow cytometry. The LDF assay can be used to characterize LD formation in human intestinal epithelial cells, or to study human (genetic) disorders that affect LD metabolism, such as DGAT1 deficiency. Furthermore, this assay can also be used in a high-throughput pipeline to test novel therapeutic compounds, which restore defects in LD formation in intestinal or other types of organoids.

Published
2019
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21. Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

Author

Schreurs, Renée R C E, Baumdick, Martin E, Sagebiel, Adrian F, Kaufmann, Max, Mokry, Michal, Klarenbeek, Paul L, Schaltenberg, Nicola, Steinert, Fenja L, van Rijn, Jorik M, Drewniak, Agata, The, Sarah-May M L, Bakx, Roel, Derikx, Joep P M, de Vries, Niek, Corpeleijn, Willemijn E, Pals, Steven T, Gagliani, Nicola, Friese, Manuel A, Middendorp, Sabine, Nieuwenhuis, Edward E S, Reinshagen, Konrad, Geijtenbeek, Teunis B H, van Goudoever, Johannes B, Bunders, Madeleine J, Schreurs, Renée R C E, Baumdick, Martin E, Sagebiel, Adrian F, Kaufmann, Max, Mokry, Michal, Klarenbeek, Paul L, Schaltenberg, Nicola, Steinert, Fenja L, van Rijn, Jorik M, Drewniak, Agata, The, Sarah-May M L, Bakx, Roel, Derikx, Joep P M, de Vries, Niek, Corpeleijn, Willemijn E, Pals, Steven T, Gagliani, Nicola, Friese, Manuel A, Middendorp, Sabine, Nieuwenhuis, Edward E S, Reinshagen, Konrad, Geijtenbeek, Teunis B H, van Goudoever, Johannes B, and Bunders, Madeleine J

Published
2019

23. DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells[S]

Author

Child Health, MDL onderzoek 2, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, MDL onderzoek 1, Infection & Immunity, Zorg en O&O, MDL, Onderzoek, van Rijn, Jorik M, van Hoesel, Marliek, de Heus, Cecilia, van Vugt, Anke H M, Klumperman, Judith, Nieuwenhuis, Edward, Houwen, Roderick H J, Middendorp, Sabine, Child Health, MDL onderzoek 2, Cancer, CMM Groep Klumperman, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, MDL onderzoek 1, Infection & Immunity, Zorg en O&O, MDL, Onderzoek, van Rijn, Jorik M, van Hoesel, Marliek, de Heus, Cecilia, van Vugt, Anke H M, Klumperman, Judith, Nieuwenhuis, Edward, Houwen, Roderick H J, and Middendorp, Sabine

Published
2019

27. Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

Author

Schreurs, Renée R.C.E., primary, Baumdick, Martin E., additional, Sagebiel, Adrian F., additional, Kaufmann, Max, additional, Mokry, Michal, additional, Klarenbeek, Paul L., additional, Schaltenberg, Nicola, additional, Steinert, Fenja L., additional, van Rijn, Jorik M., additional, Drewniak, Agata, additional, The, Sarah-May M.L., additional, Bakx, Roel, additional, Derikx, Joep P.M., additional, de Vries, Niek, additional, Corpeleijn, Willemijn E., additional, Pals, Steven T., additional, Gagliani, Nicola, additional, Friese, Manuel A., additional, Middendorp, Sabine, additional, Nieuwenhuis, Edward E.S., additional, Reinshagen, Konrad, additional, Geijtenbeek, Teunis B.H., additional, van Goudoever, Johannes B., additional, and Bunders, Madeleine J., additional

Published
2019
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28. Stem Cells are the Principal Intestinal Epithelial Responders to Bacterial Antigens

Author

Meddens, Claartje A., primary, de Vries, Maaike H., additional, Hijma, Hemme J., additional, Berrens, Anne Claire, additional, Westendorp, Bart, additional, van der Spek, Jet, additional, Kooiman, Berend A. P., additional, Schreurs, Renée R. C. E., additional, Lijster, Erik, additional, Prelic, Sinisa, additional, Nieuwenhuis, Ninke M., additional, Mijnders, Marjolein, additional, Vega, Miguel, additional, Jansen, Suze A., additional, Hanemaaijer, Evelyn S., additional, Lansu, Nico, additional, van den Dungen, Noortje A. M., additional, Bunders, Madeleine J., additional, Middendorp, Sabine, additional, Clevers, Hans, additional, Mokry, Michal, additional, and Nieuwenhuis, Edward E. S., additional

Published
2019
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29. Women in Translational Medicine: Tools to Break the Glass Ceiling

Author

Bots, Sophie H., primary, Zuidgeest, Mira G. P., additional, Gohar, Aisha, additional, Eikendal, Anouk L. M., additional, Petrelli, Alessandra, additional, van Os-Medendorp, Harmieke, additional, van der Schaaf, Marieke F., additional, van Sorge, Nina M., additional, van Wijk, Myriam, additional, Middendorp, Sabine, additional, Speksnijder, Caroline M., additional, Klipstein-Grobusch, Kerstin, additional, Seyfert-Margolis, Vicky, additional, Mollema, Esther, additional, van Wijk, Femke, additional, and den Ruijter, Hester M., additional

Published
2018
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30. Women in Translational Medicine: Tools to Break the Glass Ceiling

Author

Bots, Sophie H., Zuidgeest, Mira G. P., Gohar, Aisha, Eikendal, Anouk L. M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, den Ruijter, Hester M., Bots, Sophie H., Zuidgeest, Mira G. P., Gohar, Aisha, Eikendal, Anouk L. M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, and den Ruijter, Hester M.

Published
2018

32. Women in translational medicine: Tools to break the glass ceiling

Author

Education and Learning: Development in Interaction, Afd Pharmacoepi & Clinical Pharmacology, Leerstoel van Gog, Bots, Sophie H., Zuidgeest, Mira G.P., Gohar, Aisha, Eikendal, Anouk L.M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, den Ruijter, Hester M., Education and Learning: Development in Interaction, Afd Pharmacoepi & Clinical Pharmacology, Leerstoel van Gog, Bots, Sophie H., Zuidgeest, Mira G.P., Gohar, Aisha, Eikendal, Anouk L.M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, and den Ruijter, Hester M.

Published
2018

33. Intestinal failure and aberrant lipid metabolism in patients with DGAT1 deficiency

Author

Onderzoek, dCSCA RMSC-1, Sub Biomolecular analysis, van Rijn, Jorik M, Ardy, Rico Chandra, Kuloğlu, Zarife, Härter, Bettina, van Haaften-Visser, Désirée Y, van der Doef, Hubert P J, van Hoesel, Marliek, Kansu, Aydan, van Vugt, Anke H M, Ng, Marini, Kokke, Freddy T M, Krolo, Ana, Başaran, Meryem Keçeli, Kaya, Neslihan Gurcan, Ünlüsoy Aksu, Aysel, Dalgıç, Buket, Ozcay, Figen, Baris, Zeren, Kain, Renate, Stigter, Edwin C A, Lichtenbelt, Klaske D, Massink, Maarten P G, Duran, Karen J, Verheij, Joke B G M, Lugtenberg, Dorien, Nikkels, Peter G J, Brouwer, Henricus G F, Verkade, Henkjan J, Scheenstra, Rene, Spee, Bart, Nieuwenhuis, Edward E S, Coffer, Paul J, Janecke, Andreas R, van Haaften, Gijs, Houwen, Roderick H J H, Müller, Thomas, Middendorp, Sabine, Boztug, Kaan, Onderzoek, dCSCA RMSC-1, Sub Biomolecular analysis, van Rijn, Jorik M, Ardy, Rico Chandra, Kuloğlu, Zarife, Härter, Bettina, van Haaften-Visser, Désirée Y, van der Doef, Hubert P J, van Hoesel, Marliek, Kansu, Aydan, van Vugt, Anke H M, Ng, Marini, Kokke, Freddy T M, Krolo, Ana, Başaran, Meryem Keçeli, Kaya, Neslihan Gurcan, Ünlüsoy Aksu, Aysel, Dalgıç, Buket, Ozcay, Figen, Baris, Zeren, Kain, Renate, Stigter, Edwin C A, Lichtenbelt, Klaske D, Massink, Maarten P G, Duran, Karen J, Verheij, Joke B G M, Lugtenberg, Dorien, Nikkels, Peter G J, Brouwer, Henricus G F, Verkade, Henkjan J, Scheenstra, Rene, Spee, Bart, Nieuwenhuis, Edward E S, Coffer, Paul J, Janecke, Andreas R, van Haaften, Gijs, Houwen, Roderick H J H, Müller, Thomas, Middendorp, Sabine, and Boztug, Kaan

Published
2018

34. Women in Translational Medicine: Tools to Break the Glass Ceiling

Author

Global Health, Experimentele Afd. Cardiologie 1, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Afdeling Dermatologie/Allergologie, Infection & Immunity, Expertisecentrum Alg., MMB Research line 1, MDL onderzoek 2, Onderzoek, Child Health, Regenerative Medicine and Stem Cells, MS Hoofd-Hals Chirurgische Oncologie, MKA/BT Onderzoek, Epi Kanker Team 1, Cancer, JC onderzoeksprogramma Kanker, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CTI Van Wijk, Bots, Sophie H., Zuidgeest, Mira G. P., Gohar, Aisha, Eikendal, Anouk L. M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, den Ruijter, Hester M., Global Health, Experimentele Afd. Cardiologie 1, Onderzoek Vrouw Hart & Vaatziekten, Circulatory Health, Afdeling Dermatologie/Allergologie, Infection & Immunity, Expertisecentrum Alg., MMB Research line 1, MDL onderzoek 2, Onderzoek, Child Health, Regenerative Medicine and Stem Cells, MS Hoofd-Hals Chirurgische Oncologie, MKA/BT Onderzoek, Epi Kanker Team 1, Cancer, JC onderzoeksprogramma Kanker, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, CTI Van Wijk, Bots, Sophie H., Zuidgeest, Mira G. P., Gohar, Aisha, Eikendal, Anouk L. M., Petrelli, Alessandra, van Os-Medendorp, Harmieke, van der Schaaf, Marieke F., van Sorge, Nina M., van Wijk, Myriam, Middendorp, Sabine, Speksnijder, Caroline M., Klipstein-Grobusch, Kerstin, Seyfert-Margolis, Vicky, Mollema, Esther, van Wijk, Femke, and den Ruijter, Hester M.

Published
2018

35. Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency

Author

Regenerative Medicine and Stem Cells, MDL onderzoek 2, Child Health, MDL onderzoek 1, CMM Sectie Molecular Cancer Research, CMM Groep Burgering, Cancer, Genetica Klinische Genetica, Genetica Groep Van Haaften, Pathologie Pathologen staf, Zorg en O&O, Infection & Immunity, CMM Sectie Stem Cells, Immunologie onderzoek 2, Onderzoek, CMM Sectie Genomics and Bioinformatics, MDL patientenzorg, van Rijn, Jorik M., Ardy, Rico Chandra, Kuloğlu, Zarife, Härter, Bettina, van Haaften-Visser, Désirée Y., van der Doef, Hubert P.J., van Hoesel, Marliek, Kansu, Aydan, van Vugt, Anke H.M., Thian, Marini, Kokke, Freddy T.M., Krolo, Ana, Başaran, Meryem Keçeli, Kaya, Neslihan Gurcan, Aksu, Aysel Ünlüsoy, Dalgıç, Buket, Ozcay, Figen, Baris, Zeren, Kain, Renate, Stigter, Edwin C.A., Lichtenbelt, Klaske D., Massink, Maarten P.G., Duran, Karen J., Verheij, Joke B.G.M., Lugtenberg, Dorien, Nikkels, Peter G.J., Brouwer, Henricus G.F., Verkade, Henkjan J., Scheenstra, René, Spee, Bart, Nieuwenhuis, Edward E.S., Coffer, Paul J., Janecke, Andreas R., van Haaften, Gijs, Houwen, Roderick H.J., Müller, Thomas, Middendorp, Sabine, Boztug, Kaan, Regenerative Medicine and Stem Cells, MDL onderzoek 2, Child Health, MDL onderzoek 1, CMM Sectie Molecular Cancer Research, CMM Groep Burgering, Cancer, Genetica Klinische Genetica, Genetica Groep Van Haaften, Pathologie Pathologen staf, Zorg en O&O, Infection & Immunity, CMM Sectie Stem Cells, Immunologie onderzoek 2, Onderzoek, CMM Sectie Genomics and Bioinformatics, MDL patientenzorg, van Rijn, Jorik M., Ardy, Rico Chandra, Kuloğlu, Zarife, Härter, Bettina, van Haaften-Visser, Désirée Y., van der Doef, Hubert P.J., van Hoesel, Marliek, Kansu, Aydan, van Vugt, Anke H.M., Thian, Marini, Kokke, Freddy T.M., Krolo, Ana, Başaran, Meryem Keçeli, Kaya, Neslihan Gurcan, Aksu, Aysel Ünlüsoy, Dalgıç, Buket, Ozcay, Figen, Baris, Zeren, Kain, Renate, Stigter, Edwin C.A., Lichtenbelt, Klaske D., Massink, Maarten P.G., Duran, Karen J., Verheij, Joke B.G.M., Lugtenberg, Dorien, Nikkels, Peter G.J., Brouwer, Henricus G.F., Verkade, Henkjan J., Scheenstra, René, Spee, Bart, Nieuwenhuis, Edward E.S., Coffer, Paul J., Janecke, Andreas R., van Haaften, Gijs, Houwen, Roderick H.J., Müller, Thomas, Middendorp, Sabine, and Boztug, Kaan

Published
2018

36. Intestinal epithelial cell polarity defects in disease: lessons from microvillus inclusion disease

Author

MDL onderzoek 2, Zorg en O&O, Infection & Immunity, Child Health, Regenerative Medicine and Stem Cells, Schneeberger, Kerstin, Roth, Sabrina, Nieuwenhuis, Edward E. S., Middendorp, Sabine, MDL onderzoek 2, Zorg en O&O, Infection & Immunity, Child Health, Regenerative Medicine and Stem Cells, Schneeberger, Kerstin, Roth, Sabrina, Nieuwenhuis, Edward E. S., and Middendorp, Sabine

Published
2018

38. Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations

Author

Vogel, Georg F., primary, van Rijn, Jorik M., additional, Krainer, Iris M., additional, Janecke, Andreas R., additional, Posovzsky, Carsten, additional, Cohen, Marta, additional, Searle, Claire, additional, Jantchou, Prevost, additional, Escher, Johanna C., additional, Patey, Natalie, additional, Cutz, Ernest, additional, Müller, Thomas, additional, Middendorp, Sabine, additional, Hess, Michael W., additional, and Huber, Lukas A., additional

Published
2017
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41. Novel approaches- Tissue engineering and stem cells: In vitro modelling of the gut

Author

Regenerative Medicine and Stem Cells, Child Health, MDL onderzoek 2, Metabole ziekten patientenzorg, Zorg en O&O, Infection & Immunity, van Rijn, Jorik M, Schneeberger, Kerstin, Wiegerinck, Caroline L, Nieuwenhuis, Edward E S, Middendorp, Sabine, Regenerative Medicine and Stem Cells, Child Health, MDL onderzoek 2, Metabole ziekten patientenzorg, Zorg en O&O, Infection & Immunity, van Rijn, Jorik M, Schneeberger, Kerstin, Wiegerinck, Caroline L, Nieuwenhuis, Edward E S, and Middendorp, Sabine

Published
2016

42. Tissue-specific mutation accumulation in human adult stem cells during life

Author

CMM, CMM Groep Cuppen, Hubrecht Institute with UMC, Genetica Sectie Genoomdiagnostiek, Genetica Medische Informatica, MDL onderzoek 3, Child Health, MDL onderzoek 2, Regenerative Medicine and Stem Cells, Zorg en O&O, Infection & Immunity, Verpleegafd Vaatchirurgie D4 Oost, AIOS Anesthesiologie, CMM Sectie Molecular Cancer Research, Cancer, Circulatory Health, Brain, CMM Sectie Genomics and Bioinformatics, Blokzijl, Francis, De Ligt, Joep, Jager, Myrthe, Sasselli, Valentina, Roerink, Sophie, Sasaki, Nobuo, Huch, Meritxell, Boymans, Sander, Kuijk, Ewart, Prins, Pjotr, Nijman, Isaäc, Martincorena, Inigo, Mokry, Michal, Wiegerinck, Caroline L., Middendorp, Sabine, Sato, Toshiro, Schwank, Gerald, Nieuwenhuis, Edward E S, Verstegen, Monique M A, Van Der Laan, Luc J W, De Jonge, Jeroen, Ijzermans, Jan N M, Vries, Robert G., van de Wetering, Marc, Stratton, Michael R., Clevers, Hans, Cuppen, Edwin, Van Boxtel, Ruben, CMM, CMM Groep Cuppen, Hubrecht Institute with UMC, Genetica Sectie Genoomdiagnostiek, Genetica Medische Informatica, MDL onderzoek 3, Child Health, MDL onderzoek 2, Regenerative Medicine and Stem Cells, Zorg en O&O, Infection & Immunity, Verpleegafd Vaatchirurgie D4 Oost, AIOS Anesthesiologie, CMM Sectie Molecular Cancer Research, Cancer, Circulatory Health, Brain, CMM Sectie Genomics and Bioinformatics, Blokzijl, Francis, De Ligt, Joep, Jager, Myrthe, Sasselli, Valentina, Roerink, Sophie, Sasaki, Nobuo, Huch, Meritxell, Boymans, Sander, Kuijk, Ewart, Prins, Pjotr, Nijman, Isaäc, Martincorena, Inigo, Mokry, Michal, Wiegerinck, Caroline L., Middendorp, Sabine, Sato, Toshiro, Schwank, Gerald, Nieuwenhuis, Edward E S, Verstegen, Monique M A, Van Der Laan, Luc J W, De Jonge, Jeroen, Ijzermans, Jan N M, Vries, Robert G., van de Wetering, Marc, Stratton, Michael R., Clevers, Hans, Cuppen, Edwin, and Van Boxtel, Ruben

Published
2016

43. An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

Author

Onderzoek, Faculteit Diergeneeskunde, Schneeberger, Kerstin, Vogel, Georg F, Teunissen, Hans, van Ommen, Domenique D, Begthel, Harry, El Bouazzaoui, Layla, van Vugt, Anke H M, Beekman, Jeffrey M, Klumperman, Judith, Müller, Thomas, Janecke, Andreas, Gerner, Patrick, Huber, Lukas A, Hess, Michael W, Clevers, Hans, van Es, Johan H, Nieuwenhuis, Edward E S, Middendorp, Sabine, Onderzoek, Faculteit Diergeneeskunde, Schneeberger, Kerstin, Vogel, Georg F, Teunissen, Hans, van Ommen, Domenique D, Begthel, Harry, El Bouazzaoui, Layla, van Vugt, Anke H M, Beekman, Jeffrey M, Klumperman, Judith, Müller, Thomas, Janecke, Andreas, Gerner, Patrick, Huber, Lukas A, Hess, Michael W, Clevers, Hans, van Es, Johan H, Nieuwenhuis, Edward E S, and Middendorp, Sabine

Published
2015

44. An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

Author

Regenerative Medicine and Stem Cells, Beekman, Child Health, Infection & Immunity, CMM Sectie Celbiologie, Cancer, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Zorg en O&O, MDL onderzoek 2, Schneeberger, Kerstin, Vogel, Georg F., Teunissen, Hans, Zomer-van Ommen, Domenique, Begthel, Harry, El Bouazzaoui, Layla, van Vugt, Anke H. M., Beekman, JM, Klumperman, Judith, Mueller, Thomas, Janecke, Andreas, Gerner, Patrick, Huber, Lukas A., Hess, Michael W., Clevers, Hans, van Es, Johan H., Nieuwenhuis, Edward E. S., Middendorp, Sabine, Regenerative Medicine and Stem Cells, Beekman, Child Health, Infection & Immunity, CMM Sectie Celbiologie, Cancer, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Zorg en O&O, MDL onderzoek 2, Schneeberger, Kerstin, Vogel, Georg F., Teunissen, Hans, Zomer-van Ommen, Domenique, Begthel, Harry, El Bouazzaoui, Layla, van Vugt, Anke H. M., Beekman, JM, Klumperman, Judith, Mueller, Thomas, Janecke, Andreas, Gerner, Patrick, Huber, Lukas A., Hess, Michael W., Clevers, Hans, van Es, Johan H., Nieuwenhuis, Edward E. S., and Middendorp, Sabine

Published
2015

47. Novel approaches: Tissue engineering and stem cells – In vitromodelling of the gut

Author

van Rijn, Jorik M., Schneeberger, Kerstin, Wiegerinck, Caroline L., Nieuwenhuis, Edward E.S., and Middendorp, Sabine

Abstract

In many intestinal diseases, the function of the epithelial lining is impaired. In this review, we describe the recent developments of in vitrointestinal stem cell cultures. When these stem cells are grown in 3D structures (organoids), they provide a model of the intestinal epithelium, which is closely similar to the growth and development of the in vivogut. This model provides a new tool to study various diseases of malabsorption in functional detail and therapeutic applications, which could not be achieved with traditional cell lines. First, we describe the organization and function of the healthy small intestinal epithelium. Then, we discuss the establishment of organoid cultures and how these structures represent the healthy epithelium. Finally, we discuss organoid cultures as a tool for studying intrinsic properties of the epithelium, as a model for intestinal disease, and as a possible source for stem cell transplantations.

Published
2016
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48. Intestinal Organoids as a Patient-Specific Model System for Congenital Diarrheal Disorders

Author

van Rijn, J.M., Nieuwenhuis, EES, Middendorp, Sabine, and University Utrecht

Subjects
lipid droplets, Munc18-2, intestinal epithelium, diarrheal disorders, intestine, organoids, DGAT, ANTXR2
Abstract

Without our intestines, we would not survive. They extract nutrients from our food, and take-up electrolytes and water from what we eat and drink. To regulate all of these processes, the intestinal wall produces a mixture of substances which are needed to get this done. Furthermore, the intestine is the first line of defense against pathogens which enter our digestive system as well. All of this complex machinery is largely regulated by a single sheet of cells, the intestinal epithelium. If, despite everything, this epithelium still gets damaged, it is usually quickly restored by rapidly dividing stem cells. Sometimes, however, a child is born with a genetic defect which results in an inability of the epithelium to establish or restore its balance. In severe cases this causes vomiting, diarrhea, and a shortage of nutrients and water. Sometimes this defect is unfortunately severe enough to become life-threatening to the child. Since these disorders occur only rarely, we often do not know exactly what mechanically goes wrong, let alone how we can treat such a disease. Luckily, a technology was developed in Utrecht about ten years ago which made it possible to grow living intestinal stem cells in the laboratory, as so-called mini-guts. This development enabled us for the first time to study live intestinal cells with rare genetic defects in the lab. My thesis describes how we used these mini-guts to study intestines of children with three rare intestinal disorders. Our research led to a better understanding of the detailed mechanism of disease, and with that might bring us one step closer to a treatment for these rare diseases.

Published
2019

49. Human Fetal TNF-α-Cytokine-Producing CD4 + Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life.

Author

Schreurs RRCE, Baumdick ME, Sagebiel AF, Kaufmann M, Mokry M, Klarenbeek PL, Schaltenberg N, Steinert FL, van Rijn JM, Drewniak A, The SML, Bakx R, Derikx JPM, de Vries N, Corpeleijn WE, Pals ST, Gagliani N, Friese MA, Middendorp S, Nieuwenhuis EES, Reinshagen K, Geijtenbeek TBH, van Goudoever JB, and Bunders MJ

Subjects
Animals, CD4-Positive T-Lymphocytes metabolism, Epithelial Cells cytology, Epithelial Cells immunology, Epithelial Cells metabolism, Female, Fetus metabolism, Humans, Infant, Newborn, Intestinal Mucosa embryology, Intestinal Mucosa growth & development, Intestinal Mucosa immunology, Intestines embryology, Intestines growth & development, Mice, Inbred C57BL, Pregnancy, Stem Cells cytology, Stem Cells immunology, Stem Cells metabolism, Th1 Cells immunology, Th1 Cells metabolism, Tumor Necrosis Factor-alpha metabolism, CD4-Positive T-Lymphocytes immunology, Fetus immunology, Immunologic Memory immunology, Intestines immunology, Tumor Necrosis Factor-alpha immunology
Abstract

Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α) + CD4 + CD69 + T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4 + T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4 + T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4 + Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-α-producing CD4 + T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
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