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Start Over Descriptor "45/100" Journal nature cell biology
2 results on '"45/100"'

1. Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction

Author

Dick W. Zijlmans, Irene Talon, Sigrid Verhelst, Adam Bendall, Karlien Van Nerum, Alok Javali, Andrew A. Malcolm, Sam S. F. A. van Knippenberg, Laura Biggins, San Kit To, Adrian Janiszewski, Danielle Admiraal, Ruth Knops, Nikky Corthout, Bradley P. Balaton, Grigorios Georgolopoulos, Amitesh Panda, Natarajan V. Bhanu, Amanda J. Collier, Charlene Fabian, Ryan N. Allsop, Joel Chappell, Thi Xuan Ai Pham, Michael Oberhuemer, Cankat Ertekin, Lotte Vanheer, Paraskevi Athanasouli, Frederic Lluis, Dieter Deforce, Joop H. Jansen, Benjamin A. Garcia, Michiel Vermeulen, Nicolas Rivron, Maarten Dhaenens, Hendrik Marks, Peter J. Rugg-Gunn, Vincent Pasque, Talon, Irene [0000-0002-5800-5555], Verhelst, Sigrid [0000-0002-6791-3782], Bendall, Adam [0000-0002-6865-2625], Van Nerum, Karlien [0000-0002-8952-5473], Malcolm, Andrew A [0000-0001-6240-7701], van Knippenberg, Sam SFA [0000-0001-5656-3046], To, San Kit [0000-0002-3057-2902], Balaton, Bradley P [0000-0002-5130-7868], Panda, Amitesh [0000-0002-2702-3494], Pham, Thi Xuan Ai [0000-0003-3866-2002], Oberhuemer, Michael [0000-0003-2273-2782], Deforce, Dieter [0000-0002-0635-661X], Vermeulen, Michiel [0000-0003-0836-6894], Rivron, Nicolas [0000-0003-1590-5964], Dhaenens, Maarten [0000-0002-9801-3509], Marks, Hendrik [0000-0002-4198-3731], Rugg-Gunn, Peter J [0000-0002-9601-5949], Pasque, Vincent [0000-0002-5129-0146], Apollo - University of Cambridge Repository, and Malcolm, Andrew [0000-0001-6240-7701]

Subjects
CHROMATIN, EXPRESSION, DYNAMICS, Pluripotent Stem Cells, 631/136/2444, 101, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], PROTEIN, 13/106, BLASTOCYST, macromolecular substances, R/BIOCONDUCTOR PACKAGE, 13, PLURIPOTENCY, 14, 38/91, Histones, 13/1, All institutes and research themes of the Radboud University Medical Center, 631/337/176, Humans, TRANSCRIPTION, 96/1, 14/19, Molecular Biology, 42, Science & Technology, 45, 82/58, Proteomics and Chromatin Biology, 631/136/532/2062, article, Polycomb Repressive Complex 2, Biology and Life Sciences, Cell Differentiation, Cell Biology, NAIVE, 45/15, Chromatin, Trophoblasts, 13/31, 13/51, 14/63, 631/337/100, 38/39, 45/100, EMBRYONIC STEM-CELLS, Life Sciences & Biomedicine
Abstract

Funder: The Marks lab is supported by an NWO-XS grant, Funder: M.V. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society, Funder: D.W.Z. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society, Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.

Published
2022

2. Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration

Author

Nadine Obier, Sagar, Rita Rebollo, Jan Rehwinkel, Natalie Kehrer, Ibrahim Avsar Ilik, Dominic Grün, Daniel Maticzka, Aikaterini Polyzou, Mariana Galvão Ferrarini, Veronica Bergo, Thomas Clapes, Nina Cabezas-Wallscheid, Barbara Hummel, Anne Bridgeman, Lhéanna Klaeylé, Stylianos Lefkopoulos, Eirini Trompouki, Josip S. Herman, Asifa Akhtar, Shannon McKinney-Freeman, Pia Prater, Antonio Morales-Hernández, Ritwick Sawarkar, Rolf Backofen, Clapes, Thomas [0000-0002-2578-0563], Ferrarini, Mariana Galvao [0000-0002-9574-9991], Kehrer, Natalie [0000-0003-2412-1889], Lefkopoulos, Stylianos [0000-0003-4413-0379], Herman, Josip S. [0000-0002-1735-0846], Rehwinkel, Jan [0000-0003-3841-835X], McKinney-Freeman, Shannon [0000-0001-8061-2557], Backofen, Rolf [0000-0001-8231-3323], Akhtar, Asifa [0000-0001-8973-6193], Cabezas-Wallscheid, Nina [0000-0003-0870-0530], Grün, Dominic [0000-0002-3364-5898], Trompouki, Eirini [0000-0002-7242-8810], Apollo - University of Cambridge Repository, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Herman, Josip S [0000-0002-1735-0846]

Subjects
Interferon-Induced Helicase, IFIH1, 96, Quiescence, 13, Ligands, 631/532/2443, 96/31, 14, 13/1, 0302 clinical medicine, Cellular Senescence, 64, Mice, Knockout, 0303 health sciences, Gene knockdown, Haematopoietic stem cells, article, 45/77, Publisher Correction, 96/63, 3. Good health, Chromatin, Cell biology, Haematopoiesis, 631/136/232, [SDV.IMM]Life Sciences [q-bio]/Immunology, 64/60, 45/100, Signal transduction, Stem cell, 631/532/489, Signal Transduction, Biology, 38, 03 medical and health sciences, Animals, Humans, Regeneration, 030304 developmental biology, Cell Proliferation, 45/91, Innate immune system, 45, Regeneration (biology), HEK 293 cells, Endogenous Retroviruses, Cell Biology, Myeloablative Agonists, Chromatin Assembly and Disassembly, Hematopoietic Stem Cells, 631/532/1542, Hematopoiesis, Enzyme Activation, Mice, Inbred C57BL, HEK293 Cells, Long Interspersed Nucleotide Elements, 13/51, DNA Transposable Elements, 030217 neurology & neurosurgery
Abstract

Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5−/− HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence., Clapes et al. show that chemotherapy leads to chromatin reorganization and increased expression of transposable elements, which promote an MDA5-driven inflammatory response that enhances haematopoietic regeneration.

Published
2020

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