Search

Your search keyword '"van der Linden, Reinier"' showing total 140 results
Start Over Author "van der Linden, Reinier"
140 results on '"van der Linden, Reinier"'

2. PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Author

Sá da Bandeira, Diana, Kilpatrick, Alastair Morris, Marques, Madalena, Gomez-Salazar, Mario, Ventura, Telma, Gonzalez, Zaniah Nashira, Stefancova, Dorota, Rossi, Fiona, Vermeren, Matthieu, Vink, Chris Sebastiaan, Beltran, Mariana, Henderson, Neil Cowan, Jung, Bongnam, van der Linden, Reinier, van de Werken, Harmen Jan George, van Ijcken, Wilfred F.J., Betsholtz, Christer, Forbes, Stuart John, Cuervo, Henar, and Crisan, Mihaela

Published
2022
Full Text
View/download PDF

3. High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Author

Beumer, Joep, Puschhof, Jens, Bauzá-Martinez, Julia, Martínez-Silgado, Adriana, Elmentaite, Rasa, James, Kylie R., Ross, Alexander, Hendriks, Delilah, Artegiani, Benedetta, Busslinger, Georg A., Ponsioen, Bas, Andersson-Rolf, Amanda, Saftien, Aurelia, Boot, Charelle, Kretzschmar, Kai, Geurts, Maarten H., Bar-Ephraim, Yotam E., Pleguezuelos-Manzano, Cayetano, Post, Yorick, Begthel, Harry, van der Linden, Franka, Lopez-Iglesias, Carmen, van de Wetering, Willine J., van der Linden, Reinier, Peters, Peter J., Heck, Albert J.R., Goedhart, Joachim, Snippert, Hugo, Zilbauer, Matthias, Teichmann, Sarah A., Wu, Wei, and Clevers, Hans

Published
2020
Full Text
View/download PDF

5. Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation

Author

Lin, Lin, primary, DeMartino, Jeff, additional, Wang, Daisong, additional, van Son, Gijs J. F., additional, van der Linden, Reinier, additional, Begthel, Harry, additional, Korving, Jeroen, additional, Andersson-Rolf, Amanda, additional, van den Brink, Stieneke, additional, Lopez-Iglesias, Carmen, additional, van de Wetering, Willine J., additional, Balwierz, Aleksandra, additional, Margaritis, Thanasis, additional, van de Wetering, Marc, additional, Peters, Peter J., additional, Drost, Jarno, additional, van Es, Johan H., additional, and Clevers, Hans, additional

Published
2023
Full Text
View/download PDF

8. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

Author

Developmental Biology, Sub Developmental Biology, Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, van Oudenaarden, Alexander, Developmental Biology, Sub Developmental Biology, Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, and van Oudenaarden, Alexander

Published
2023

9. Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation

Author

Lin, Lin, DeMartino, Jeff, Wang, Daisong, van Son, Gijs J F, van der Linden, Reinier, Begthel, Harry, Korving, Jeroen, Andersson-Rolf, Amanda, van den Brink, Stieneke, Lopez-Iglesias, Carmen, van de Wetering, Willine J, Balwierz, Aleksandra, Margaritis, Thanasis, van de Wetering, Marc, Peters, Peter J, Drost, Jarno, van Es, Johan H, Clevers, Hans, Lin, Lin, DeMartino, Jeff, Wang, Daisong, van Son, Gijs J F, van der Linden, Reinier, Begthel, Harry, Korving, Jeroen, Andersson-Rolf, Amanda, van den Brink, Stieneke, Lopez-Iglesias, Carmen, van de Wetering, Willine J, Balwierz, Aleksandra, Margaritis, Thanasis, van de Wetering, Marc, Peters, Peter J, Drost, Jarno, van Es, Johan H, and Clevers, Hans

Abstract

Enteroendocrine cells (EECs) are hormone-producing cells residing in the epithelium of stomach, small intestine (SI), and colon. EECs regulate aspects of metabolic activity, including insulin levels, satiety, gastrointestinal secretion, and motility. The generation of different EEC lineages is not completely understood. In this work, we report a CRISPR knockout screen of the entire repertoire of transcription factors (TFs) in adult human SI organoids to identify dominant TFs controlling EEC differentiation. We discovered ZNF800 as a master repressor for endocrine lineage commitment, which particularly restricts enterochromaffin cell differentiation by directly controlling an endocrine TF network centered on PAX4. Thus, organoid models allow unbiased functional CRISPR screens for genes that program cell fate.

Published
2023

10. Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation

Author

Groep Holstege, Hubrecht Institute with UMC, CMM, Cancer, Lin, Lin, DeMartino, Jeff, Wang, Daisong, van Son, Gijs J.F., van der Linden, Reinier, Begthel, Harry, Korving, Jeroen, Andersson-Rolf, Amanda, den Brink, Stieneke van, Lopez-Iglesias, Carmen, van de Wetering, Willine J., Balwierz, Aleksandra, Margaritis, Thanasis, van de Wetering, Marc, Peters, Peter J., Drost, Jarno, van Es, Johan H., Clevers, Hans, Groep Holstege, Hubrecht Institute with UMC, CMM, Cancer, Lin, Lin, DeMartino, Jeff, Wang, Daisong, van Son, Gijs J.F., van der Linden, Reinier, Begthel, Harry, Korving, Jeroen, Andersson-Rolf, Amanda, den Brink, Stieneke van, Lopez-Iglesias, Carmen, van de Wetering, Willine J., Balwierz, Aleksandra, Margaritis, Thanasis, van de Wetering, Marc, Peters, Peter J., Drost, Jarno, van Es, Johan H., and Clevers, Hans

Published
2023

11. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

Author

CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, van Oudenaarden, Alexander, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, and van Oudenaarden, Alexander

Published
2023

14. PDGFR beta(+) cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Author

da Bandeira, Diana Sa, Kilpatrick, Alastair Morris, Marques, Madalena, Gomez-Salazar, Mario, Ventura, Telma, Gonzalez, Zaniah Nashira, Stefancova, Dorota, Rossi, Fiona, Vermeren, Matthieu, Vink, Chris Sebastiaan, Beltran, Mariana, Henderson, Neil Cowan, Jung, Bongnam, van der Linden, Reinier, van de Werken, Harmen Jan George, van Ijcken, Wilfred F. J., Betsholtz, Christer, Forbes, Stuart John, Cuervo, Henar, Crisan, Mihaela, da Bandeira, Diana Sa, Kilpatrick, Alastair Morris, Marques, Madalena, Gomez-Salazar, Mario, Ventura, Telma, Gonzalez, Zaniah Nashira, Stefancova, Dorota, Rossi, Fiona, Vermeren, Matthieu, Vink, Chris Sebastiaan, Beltran, Mariana, Henderson, Neil Cowan, Jung, Bongnam, van der Linden, Reinier, van de Werken, Harmen Jan George, van Ijcken, Wilfred F. J., Betsholtz, Christer, Forbes, Stuart John, Cuervo, Henar, and Crisan, Mihaela

Abstract

Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFR beta signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFR beta is involved. Here, we show that PDGFR beta is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFR beta(+) cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFR beta(+) embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.

Published
2022
Full Text
View/download PDF

15. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

Author

Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, van Oudenaarden, Alexander, Zeller, Peter, Yeung, Jake, Viñas Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, and van Oudenaarden, Alexander

Abstract

Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.

Published
2022

16. 3060 – PDGFRΒ+ CELLS PLAY A DUAL ROLE AS HEMATOPOIETIC PRECURSORS AND NICHE CELLS DURING MOUSE ONTOGENY

Author

Crisan, Mihaela, primary, da bandeira, Diana Sa, additional, Kilpatrick, Alastair, additional, Marques, Madalena, additional, Gomez-salazar, Mario, additional, Ventura, Telma, additional, Gonzalez, Zaniah, additional, Stefancova, Dorota, additional, Rossi, Fiona, additional, Vink, Chris, additional, Beltran, Mariana, additional, Henderson, Neil, additional, Jung, Bongnam, additional, Van Der Linden, Reinier, additional, Werken, Harmen Van De, additional, Van IJcken, Wilfred, additional, Betsholtz, Christer, additional, Forbes, Stuart, additional, and Cuervo, Henar, additional

Published
2022
Full Text
View/download PDF

17. Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development

Author

Robin, Catherine, Bollerot, Karine, Mendes, Sandra, Haak, Esther, Crisan, Mihaela, Cerisoli, Francesco, Lauw, Ivoune, Kaimakis, Polynikis, Jorna, Ruud, Vermeulen, Mark, Kayser, Manfred, van der Linden, Reinier, Imanirad, Parisa, Verstegen, Monique, Nawaz-Yousaf, Humaira, Papazian, Natalie, Steegers, Eric, Cupedo, Tom, and Dzierzak, Elaine

Published
2009
Full Text
View/download PDF

19. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, Behjati, Sam, Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, and Behjati, Sam

Abstract

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.

Published
2021

20. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Afd Pharmaceutics, Pharmaceutics, Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, Behjati, Sam, Afd Pharmaceutics, Pharmaceutics, Kildisiute, Gerda, Kholosy, Waleed M, Young, Matthew D, Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R, Pacyna, Clarissa N, Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M, Langenberg-Ververgaert, Karin P S, Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C P, Tas, Michelle L, Wijnen, Marc H W A, van Noesel, Max M, Del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C, Haniffa, Muzlifah, Teichmann, Sarah A, Rampling, Dyanne, Sebire, Neil J, He, Xiaoling, de Krijger, Ronald R, Barker, Roger A, Meyer, Kerstin B, Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J, and Behjati, Sam

Published
2021

21. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Groep Holstege, CTI Leusen, CMM Groep Burgering, Cancer, Zorgeenheid Kinderchirurgie Medisch, Onderzoek Beeld, Pathologie Pathologen staf, Kildisiute, Gerda, Kholosy, Waleed M., Young, Matthew D., Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R., Pacyna, Clarissa N., Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M., Langenberg-Ververgaert, Karin P.S., Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C.P., Tas, Michelle L., Wijnen, Marc H.W.A., van Noesel, Max M., del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C., Haniffa, Muzlifah, Teichmann, Sarah A., Rampling, Dyanne, Sebire, Neil J., He, Xiaoling, de Krijger, Ronald R., Barker, Roger A., Meyer, Kerstin B., Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J., Behjati, Sam, Groep Holstege, CTI Leusen, CMM Groep Burgering, Cancer, Zorgeenheid Kinderchirurgie Medisch, Onderzoek Beeld, Pathologie Pathologen staf, Kildisiute, Gerda, Kholosy, Waleed M., Young, Matthew D., Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R., Pacyna, Clarissa N., Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M., Langenberg-Ververgaert, Karin P.S., Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C.P., Tas, Michelle L., Wijnen, Marc H.W.A., van Noesel, Max M., del Valle, Ignacio, Barone, Giuseppe, van der Linden, Reinier, Duncan, Catriona, Anderson, John, Achermann, John C., Haniffa, Muzlifah, Teichmann, Sarah A., Rampling, Dyanne, Sebire, Neil J., He, Xiaoling, de Krijger, Ronald R., Barker, Roger A., Meyer, Kerstin B., Bayraktar, Omer, Straathof, Karin, Molenaar, Jan J., and Behjati, Sam

Published
2021

22. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Kildisiute, Gerda, primary, Kholosy, Waleed M., additional, Young, Matthew D., additional, Roberts, Kenny, additional, Elmentaite, Rasa, additional, van Hooff, Sander R., additional, Pacyna, Clarissa N., additional, Khabirova, Eleonora, additional, Piapi, Alice, additional, Thevanesan, Christine, additional, Bugallo-Blanco, Eva, additional, Burke, Christina, additional, Mamanova, Lira, additional, Keller, Kaylee M., additional, Langenberg-Ververgaert, Karin P.S., additional, Lijnzaad, Philip, additional, Margaritis, Thanasis, additional, Holstege, Frank C.P., additional, Tas, Michelle L., additional, Wijnen, Marc H.W.A., additional, van Noesel, Max M., additional, del Valle, Ignacio, additional, Barone, Giuseppe, additional, van der Linden, Reinier, additional, Duncan, Catriona, additional, Anderson, John, additional, Achermann, John C., additional, Haniffa, Muzlifah, additional, Teichmann, Sarah A., additional, Rampling, Dyanne, additional, Sebire, Neil J., additional, He, Xiaoling, additional, de Krijger, Ronald R., additional, Barker, Roger A., additional, Meyer, Kerstin B., additional, Bayraktar, Omer, additional, Straathof, Karin, additional, Molenaar, Jan J., additional, and Behjati, Sam, additional

Published
2021
Full Text
View/download PDF

24. Tumor to normal single cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Author

Kildisiute, Gerda, primary, Kholosy, Waleed M., additional, Young, Matthew D., additional, Roberts, Kenny, additional, Elmentaite, Rasa, additional, van Hooff, Sander R., additional, Khabirova, Eleonora, additional, Piapi, Alice, additional, Thevanesan, Christine, additional, Blanco, Eva Bugallo, additional, Burke, Christina, additional, Mamanova, Lira, additional, Lijnzaad, Philip, additional, Margaritis, Thanasis, additional, Holstege, Frank C.P., additional, Tas, Michelle L., additional, Wijnen, Marc H.W.A., additional, van Noesel, Max M., additional, del Valle, Ignacio, additional, Barone, Giuseppe, additional, van der Linden, Reinier, additional, Duncan, Catriona, additional, Anderson, John, additional, Achermann, John C., additional, Haniffa, Muzlifah, additional, Teichmann, Sarah A., additional, Rampling, Dyanne, additional, Sebire, Neil J., additional, He, Xiaoling, additional, de Krijger, Ronald R., additional, Barker, Roger A., additional, Meyer, Kerstin B., additional, Bayraktar, Omer, additional, Straathof, Karin, additional, Molenaar, Jan J., additional, and Behjati, Sam, additional

Published
2020
Full Text
View/download PDF

25. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli

Author

Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M, Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B, Paganelli, Fernanda L, Geurts, Maarten H, Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Garcia, K Christopher, Top, Janetta, Willems, Rob J L, Giannakis, Marios, Bonnet, Richard, Quirke, Phil, Meyerson, Matthew, Cuppen, Edwin, van Boxtel, Ruben, Clevers, Hans, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M, Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B, Paganelli, Fernanda L, Geurts, Maarten H, Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Garcia, K Christopher, Top, Janetta, Willems, Rob J L, Giannakis, Marios, Bonnet, Richard, Quirke, Phil, Meyerson, Matthew, Cuppen, Edwin, van Boxtel, Ruben, and Clevers, Hans

Abstract

Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

Published
2020

26. High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Author

CMM Groep Snippert, Cancer, CMM Sectie Molecular Cancer Research, Child Health, Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, Beumer, Joep, Puschhof, Jens, Bauzá-Martinez, Julia, Martínez-Silgado, Adriana, Elmentaite, Rasa, James, Kylie R, Ross, Alexander, Hendriks, Delilah, Artegiani, Benedetta, Busslinger, Georg A, Ponsioen, Bas, Andersson-Rolf, Amanda, Saftien, Aurelia, Boot, Charelle, Kretzschmar, Kai, Geurts, Maarten H, Bar-Ephraim, Yotam E, Pleguezuelos-Manzano, Cayetano, Post, Yorick, Begthel, Harry, van der Linden, Franka, Lopez-Iglesias, Carmen, van de Wetering, Willine J, van der Linden, Reinier, Peters, Peter J, Heck, Albert J R, Goedhart, Joachim, Snippert, Hugo, Zilbauer, Matthias, Teichmann, Sarah A, Wu, Wei, Clevers, Hans, CMM Groep Snippert, Cancer, CMM Sectie Molecular Cancer Research, Child Health, Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, Beumer, Joep, Puschhof, Jens, Bauzá-Martinez, Julia, Martínez-Silgado, Adriana, Elmentaite, Rasa, James, Kylie R, Ross, Alexander, Hendriks, Delilah, Artegiani, Benedetta, Busslinger, Georg A, Ponsioen, Bas, Andersson-Rolf, Amanda, Saftien, Aurelia, Boot, Charelle, Kretzschmar, Kai, Geurts, Maarten H, Bar-Ephraim, Yotam E, Pleguezuelos-Manzano, Cayetano, Post, Yorick, Begthel, Harry, van der Linden, Franka, Lopez-Iglesias, Carmen, van de Wetering, Willine J, van der Linden, Reinier, Peters, Peter J, Heck, Albert J R, Goedhart, Joachim, Snippert, Hugo, Zilbauer, Matthias, Teichmann, Sarah A, Wu, Wei, and Clevers, Hans

Published
2020

28. Cell Type Purification by Single-Cell Transcriptome-Trained Sorting

Author

Baron, Chloé S, Barve, Aditya, Muraro, Mauro J, van der Linden, Reinier, Dharmadhikari, Gitanjali, Lyubimova, Anna, de Koning, Eelco J P, van Oudenaarden, Alexander, Baron, Chloé S, Barve, Aditya, Muraro, Mauro J, van der Linden, Reinier, Dharmadhikari, Gitanjali, Lyubimova, Anna, de Koning, Eelco J P, and van Oudenaarden, Alexander

Abstract

Much of current molecular and cell biology research relies on the ability to purify cell types by fluorescence-activated cell sorting (FACS). FACS typically relies on the ability to label cell types of interest with antibodies or fluorescent transgenic constructs. However, antibody availability is often limited, and genetic manipulation is labor intensive or impossible in the case of primary human tissue. To date, no systematic method exists to enrich for cell types without a priori knowledge of cell-type markers. Here, we propose GateID, a computational method that combines single-cell transcriptomics with FACS index sorting to purify cell types of choice using only native cellular properties such as cell size, granularity, and mitochondrial content. We validate GateID by purifying various cell types from zebrafish kidney marrow and the human pancreas to high purity without resorting to specific antibodies or transgenes.

Published
2019

29. Cell Type Purification by Single-Cell Transcriptome-Trained Sorting

Author

Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Cancer, Baron, Chloé S., Barve, Aditya, Muraro, Mauro J., van der Linden, Reinier, Dharmadhikari, Gitanjali, Lyubimova, Anna, de Koning, Eelco J.P., van Oudenaarden, Alexander, Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Cancer, Baron, Chloé S., Barve, Aditya, Muraro, Mauro J., van der Linden, Reinier, Dharmadhikari, Gitanjali, Lyubimova, Anna, de Koning, Eelco J.P., and van Oudenaarden, Alexander

Published
2019

31. Mutational signature in colorectal cancer caused by genotoxic pks+E. coli.

Author

Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M., Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B., Paganelli, Fernanda L., Geurts, Maarten H., Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Genomics England Research Consortium, Ambrose, J. C., and Arumugam, P.

Abstract

Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks+ island develop a distinct mutational signature associated with colorectal cancer. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

33. Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation

Author

van der Pluijm, Ingrid, primary, Burger, Joyce, additional, van Heijningen, Paula M, additional, IJpma, Arne, additional, van Vliet, Nicole, additional, Milanese, Chiara, additional, Schoonderwoerd, Kees, additional, Sluiter, Willem, additional, Ringuette, Lea-Jeanne, additional, Dekkers, Dirk H W, additional, Que, Ivo, additional, Kaijzel, Erik L, additional, te Riet, Luuk, additional, MacFarlane, Elena G, additional, Das, Devashish, additional, van der Linden, Reinier, additional, Vermeij, Marcel, additional, Demmers, Jeroen A, additional, Mastroberardino, Pier G, additional, Davis, Elaine C, additional, Yanagisawa, Hiromi, additional, Dietz, Harry C, additional, Kanaar, Roland, additional, and Essers, Jeroen, additional

Published
2018
Full Text
View/download PDF

36. BMP signalling differentially regulates distinct haematopoietic stem cell types

Author

Crisan, Mihaela, primary, Kartalaei, Parham Solaimani, additional, Vink, Chris S., additional, Yamada-Inagawa, Tomoko, additional, Bollerot, Karine, additional, van IJcken, Wilfred, additional, van der Linden, Reinier, additional, de Sousa Lopes, Susana M. Chuva, additional, Monteiro, Rui, additional, Mummery, Christine, additional, and Dzierzak, Elaine, additional

Published
2015
Full Text
View/download PDF

37. TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

Author

Papadopoulos, Petros, primary, Gutiérrez, Laura, additional, Demmers, Jeroen, additional, Scheer, Elisabeth, additional, Pourfarzad, Farzin, additional, Papageorgiou, Dimitris N., additional, Karkoulia, Elena, additional, Strouboulis, John, additional, van de Werken, Harmen J. G., additional, van der Linden, Reinier, additional, Vandenberghe, Peter, additional, Dekkers, Dick H. W., additional, Philipsen, Sjaak, additional, Grosveld, Frank, additional, and Tora, Làszlò, additional

Published
2015
Full Text
View/download PDF

38. Whole-transcriptome analysis of endothelial to hematopoietic stem cell transition reveals a requirement for Gpr56 in HSC generation

Author

Solaimani Kartalaei, Parham, primary, Yamada-Inagawa, Tomoko, additional, Vink, Chris S., additional, de Pater, Emma, additional, van der Linden, Reinier, additional, Marks-Bluth, Jonathon, additional, van der Sloot, Anthon, additional, van den Hout, Mirjam, additional, Yokomizo, Tomomasa, additional, van Schaick-Solernó, M. Lucila, additional, Delwel, Ruud, additional, Pimanda, John E., additional, van IJcken, Wilfred F.J., additional, and Dzierzak, Elaine, additional

Published
2014
Full Text
View/download PDF

39. TAF10 Interacts with GATA1 Transcription Factor and Controls Mouse Erythropoiesis

Author

Papadopoulos, Petros, primary, Gutierrez, Laura, additional, Demmers, Jeroen, additional, Papageorgiou, Dimitris, additional, Karkoulia, Elena, additional, Strouboulis, John, additional, van der Linden, Reinier, additional, Scheer, Elisabeth, additional, Pourfarzad, Farzin, additional, Dekkers, Dick, additional, Vandenberghe, Peter, additional, Philipsen, Sjaak, additional, Grosveld, Frank, additional, and Tora, László, additional

Published
2014
Full Text
View/download PDF

41. Gata2 is required for HSC generation and survival

Author

de Pater, Emma, primary, Kaimakis, Polynikis, additional, Vink, Chris S., additional, Yokomizo, Tomomasa, additional, Yamada-Inagawa, Tomoko, additional, van der Linden, Reinier, additional, Kartalaei, Parham Solaimani, additional, Camper, Sally A., additional, Speck, Nancy, additional, and Dzierzak, Elaine, additional

Published
2013
Full Text
View/download PDF

42. Erythropoietic Defect Associated with Reduced Cell Proliferation in Mice Lacking the 26S Proteasome Shuttling Factor Rad23b

Author

Bergink, Steven, primary, Theil, Arjan F., additional, Toussaint, Wendy, additional, De Cuyper, Iris M., additional, Kulu, Divine I., additional, Clapes, Thomas, additional, van der Linden, Reinier, additional, Demmers, Jeroen A., additional, Mul, Eric P., additional, van Alphen, Floris P., additional, Marteijn, Jurgen A., additional, van Gent, Teus, additional, Maas, Alex, additional, Robin, Catherine, additional, Philipsen, Sjaak, additional, Vermeulen, Wim, additional, Mitchell, James R., additional, and Gutiérrez, Laura, additional

Published
2013
Full Text
View/download PDF

46. In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate

Author

Eich, Christina, Arlt, Jochen, Vink, Chris S., Solaimani Kartalaei, Parham, Kaimakis, Polynikis, Mariani, Samanta A., van der Linden, Reinier, van Cappellen, Wiggert A., and Dzierzak, Elaine

Abstract

Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Although Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known about the in vivo expression dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos. Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter expression in cells undergoing endothelial-to-hematopoietic transition. Moreover, Gata2 reporter pulsatile expression is dramatically altered in Gata2+/− aortic cells, which undergo fewer transitions and are reduced in hematopoietic potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a highly unstable genetic state in single cells concomitant with their transition to hematopoietic fate. This reinforces the notion that threshold levels of Gata2 influence fate establishment and has implications for transcription factor–related hematologic dysfunctions.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results