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Andreas Trumpp

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https://read.qxmd.com/read/30765776/the-long-non-coding-rna-meg3-is-dispensable-for-hematopoietic-stem-cells
#1
Pia Sommerkamp, Simon Renders, Luisa Ladel, Agnes Hotz-Wagenblatt, Katharina Schönberger, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Yunli Zhou, Anne Klibanski, Nina Cabezas-Wallscheid, Andreas Trumpp
The long non-coding RNA (lncRNA) Maternally Expressed Gene 3 (Meg3) is encoded within the imprinted Dlk1-Meg3 gene locus and is only maternally expressed. Meg3 has been shown to play an important role in the regulation of cellular proliferation and functions as a tumor suppressor in numerous tissues. Meg3 is highly expressed in mouse adult hematopoietic stem cells (HSCs) and strongly down-regulated in early progenitors. To address its functional role in HSCs, we used MxCre to conditionally delete Meg3 in the adult bone marrow of Meg3mat-flox/pat-wt mice...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30581079/identification-of-embryonic-neural-plate-border-stem-cells-and-their-generation-by-direct-reprogramming-from-adult-human-blood-cells
#2
Marc Christian Thier, Oliver Hommerding, Jasper Panten, Roberta Pinna, Diego García-González, Thomas Berger, Philipp Wörsdörfer, Yassen Assenov, Roberta Scognamiglio, Adriana Przybylla, Paul Kaschutnig, Lisa Becker, Michael D Milsom, Anna Jauch, Jochen Utikal, Carl Herrmann, Hannah Monyer, Frank Edenhofer, Andreas Trumpp
We report the direct reprogramming of both adult human fibroblasts and blood cells into induced neural plate border stem cells (iNBSCs) by ectopic expression of four neural transcription factors. Self-renewing, clonal iNBSCs can be robustly expanded in defined media while retaining multilineage differentiation potential. They generate functional cell types of neural crest and CNS lineages and could be used to model a human pain syndrome via gene editing of SCN9A in iNBSCs. NBSCs can also be derived from human pluripotent stem cells and share functional and molecular features with NBSCs isolated from embryonic day 8...
January 3, 2019: Cell Stem Cell
https://read.qxmd.com/read/30554962/deterministic-somatic-cell-reprogramming-involves-continuous-transcriptional-changes-governed-by-myc-and-epigenetic-driven-modules
#3
Asaf Zviran, Nofar Mor, Yoach Rais, Hila Gingold, Shani Peles, Elad Chomsky, Sergey Viukov, Jason D Buenrostro, Roberta Scognamiglio, Leehee Weinberger, Yair S Manor, Vladislav Krupalnik, Mirie Zerbib, Hadas Hezroni, Diego Adhemar Jaitin, David Larastiaso, Shlomit Gilad, Sima Benjamin, Ohad Gafni, Awni Mousa, Muneef Ayyash, Daoud Sheban, Jonathan Bayerl, Alejandro Aguilera-Castrejon, Rada Massarwa, Itay Maza, Suhair Hanna, Yonatan Stelzer, Igor Ulitsky, William J Greenleaf, Amos Tanay, Andreas Trumpp, Ido Amit, Yitzhak Pilpel, Noa Novershtern, Jacob H Hanna
The epigenetic dynamics of induced pluripotent stem cell (iPSC) reprogramming in correctly reprogrammed cells at high resolution and throughout the entire process remain largely undefined. Here, we characterize conversion of mouse fibroblasts into iPSCs using Gatad2a-Mbd3/NuRD-depleted and highly efficient reprogramming systems. Unbiased high-resolution profiling of dynamic changes in levels of gene expression, chromatin engagement, DNA accessibility, and DNA methylation were obtained. We identified two distinct and synergistic transcriptional modules that dominate successful reprogramming, which are associated with cell identity and biosynthetic genes...
December 10, 2018: Cell Stem Cell
https://read.qxmd.com/read/30404864/wnt1-is-an-lrp5-independent-bone-anabolic-wnt-ligand
#4
Julia Luther, Timur Alexander Yorgan, Tim Rolvien, Lorenz Ulsamer, Till Koehne, Nannan Liao, Daniela Keller, Nele Vollersen, Stefan Teufel, Mona Neven, Stephanie Peters, Michaela Schweizer, Andreas Trumpp, Sebastian Rosigkeit, Ernesto Bockamp, Stefan Mundlos, Uwe Kornak, Ralf Oheim, Michael Amling, Thorsten Schinke, Jean-Pierre David
WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice...
November 7, 2018: Science Translational Medicine
https://read.qxmd.com/read/30276763/sustained-prognostic-impact-of-circulating-tumor-cell-status-and-kinetics-upon-further-progression-of-metastatic-breast-cancer
#5
Sarah F Jauch, Sabine Riethdorf, Martin R Sprick, Florian Schütz, Birgitt Schönfisch, Sara Y Brucker, Thomas M Deutsch, Juliane Nees, Massimo Saini, Lisa M Becker, Barbara Burwinkel, Peter Sinn, Frederik Marmé, Klaus Pantel, Dirk Jäger, Christof Sohn, Andreas Trumpp, Markus Wallwiener, Andreas Schneeweiss
PURPOSE: Serial longitudinal enumeration of circulating tumor cells (CTCs) has shown its prognostic value on progression-free survival and overall survival (OS) in patients with stage IV breast cancer. This study prospectively evaluated the role of CTCs as a prognostic marker during further progression of metastatic breast cancer (MBC). METHODS: Among 476 MBC patients recruited between 2010 and 2015, the 103 patients with a known CTC status at baseline (CTCBL ) and within 4 weeks of tumor progression (CTCPD ) were included...
October 1, 2018: Breast Cancer Research and Treatment
https://read.qxmd.com/read/30222320/reactivity-of-tetrahalo-and-difluorodiboranes-4-toward-lewis-basic-platinum-0-bis-boryl-borylborato-and-doubly-boryl-bridged-platinum-complexes
#6
Jonas H Muessig, Dominic Prieschl, Andrea Deißenberger, Rian D Dewhurst, Maximilian Dietz, J Oscar C Jiménez-Halla, Alexandra Trumpp, Sunewang R Wang, Carina Brunecker, Alena Haefner, Annalena Gärtner, Torsten Thiess, Julian Böhnke, Krzysztof Radacki, Rüdiger Bertermann, Todd B Marder, Holger Braunschweig
The reaction of the tetrahalodiboranes(4) B2 F4 , B2 Cl4 , and B2 Br4 with a Lewis basic platinum(0) complex led to the isolation of the cis-bis(difluoroboryl) complex cis-[(Cy3 P)2 Pt(BF2 )2 ] (1) and the novel borylborato complexes trans-[(Cy3 P)2 Pt{B(X)-BX3 }] (2, X = Cl; 3, X = Br), respectively. The trans influence of the borylborato group was found to be one of the strongest ever observed experimentally. Furthermore, the reactivity of little-explored diaryldifluorodiboranes(4) F2 B-BMes2 and the new derivative F2 B-BAn2 (An = 9-anthryl) toward a range of platinum(0) complexes was investigated...
October 2, 2018: Journal of the American Chemical Society
https://read.qxmd.com/read/29915358/single-cell-characterization-of-haematopoietic-progenitors-and-their-trajectories-in-homeostasis-and-perturbed-haematopoiesis
#7
Amir Giladi, Franziska Paul, Yoni Herzog, Yaniv Lubling, Assaf Weiner, Ido Yofe, Diego Jaitin, Nina Cabezas-Wallscheid, Regine Dress, Florent Ginhoux, Andreas Trumpp, Amos Tanay, Ido Amit
The dynamics of haematopoietic stem cell differentiation and the hierarchy of oligopotent stem cells in the bone marrow remain controversial. Here we dissect haematopoietic progenitor populations at single cell resolution, deriving an unbiased reference model of transcriptional states in normal and perturbed murine bone marrow. We define the signature of the naive haematopoietic stem cell and find a continuum of core progenitor states. Core cell populations mix transcription of pre-myeloid and pre-lymphoid programs, but do not mix erythroid or megakaryocyte programs with other fates...
July 2018: Nature Cell Biology
https://read.qxmd.com/read/29777010/developmental-vascular-regression-is-regulated-by-a-wnt-%C3%AE-catenin-myc-and-cdkn1a-pathway-that-controls-cell-proliferation-and-cell-death
#8
Gowri Nayak, Yoshinobu Odaka, Vikram Prasad, Alyssa F Solano, Eun-Jin Yeo, Shruti Vemaraju, Jeffery D Molkentin, Andreas Trumpp, Bart Williams, Sujata Rao, Richard A Lang
Normal development requires tight regulation of cell proliferation and cell death. Here, we have investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc , and the cyclin-dependent kinase inhibitor CDKN1A (P21), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway co-receptors LRP5 and LRP6 have overlapping activities that mediate the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs)...
June 14, 2018: Development
https://read.qxmd.com/read/29769714/author-correction-a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#9
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
In the originally published version of this Letter, ref. 43 was erroneously provided twice. In the 'Estimation of relative cell-type-specific composition of AML samples' section in the Methods, the citation to ref. 43 after the GEO dataset GSE24759 is correct. However, in the 'Mice' section of the Methods, the citation to ref. 43 after 'TAMERE' should have been associated with a new reference1. The original Letter has been corrected online (with the new reference included as ref. 49).
June 2018: Nature
https://read.qxmd.com/read/29727678/causes-and-consequences-of-hematopoietic-stem-cell-heterogeneity
#10
REVIEW
Simon Haas, Andreas Trumpp, Michael D Milsom
Blood and immune cells derive from multipotent hematopoietic stem cells (HSCs). Classically, stem and progenitor populations have been considered discrete homogeneous populations. However, recent technological advances have revealed significant HSC heterogeneity, with evidence for early HSC lineage segregation and the presence of lineage-biased HSCs and lineage-restricted progenitors within the HSC compartment. These and other findings challenge many aspects of the classical view of HSC biology. We review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field...
May 3, 2018: Cell Stem Cell
https://read.qxmd.com/read/29491397/single-cell-polarity-in-liquid-phase-facilitates-tumour-metastasis
#11
Anna Lorentzen, Paul F Becker, Jan Kosla, Massimo Saini, Kathrin Weidele, Paolo Ronchi, Corinna Klein, Monika J Wolf, Felix Geist, Bastian Seubert, Marc Ringelhan, Daniela Mihic-Probst, Knud Esser, Marko Roblek, Felix Kuehne, Gaia Bianco, Tracy O'Connor, Quentin Müller, Kathleen Schuck, Sebastian Lange, Daniel Hartmann, Saskia Spaich, Olaf Groß, Jochen Utikal, Sebastian Haferkamp, Martin R Sprick, Amruta Damle-Vartak, Alexander Hapfelmeier, Norbert Hüser, Ulrike Protzer, Andreas Trumpp, Dieter Saur, Nachiket Vartak, Christoph A Klein, Bernhard Polzer, Lubor Borsig, Mathias Heikenwalder
Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients...
February 28, 2018: Nature Communications
https://read.qxmd.com/read/29440228/ampk-promotes-survival-of-c-myc-positive-melanoma-cells-by-suppressing-oxidative-stress
#12
Alain Kfoury, Marzia Armaro, Caterina Collodet, Jessica Sordet-Dessimoz, Maria Pilar Giner, Stefan Christen, Sofia Moco, Marion Leleu, Laurence de Leval, Ute Koch, Andreas Trumpp, Kei Sakamoto, Friedrich Beermann, Freddy Radtke
Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the Nras Q61K INK4a -/- mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells...
March 1, 2018: EMBO Journal
https://read.qxmd.com/read/29408233/an-intrinsic-interferon-program-protects-stem-cells-from-viral-infection
#13
COMMENT
Simon Haas, Andreas Trumpp
Specific protection mechanisms are required to safeguard stem cell integrity. In a recent issue of Cell, Wu et al. (2018) show that stem cells are equipped with high intrinsic expression of interferon-stimulated genes (ISGs) but remain refractory to acute interferon signaling. This protects stem cells from viral infection.
February 5, 2018: Developmental Cell
https://read.qxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#14
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/29342133/a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#15
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors...
January 25, 2018: Nature
https://read.qxmd.com/read/29340881/circulating-free-dna-integrity-and-concentration-as-independent-prognostic-markers-in-metastatic-breast-cancer
#16
Jie Cheng, Tim Holland-Letz, Markus Wallwiener, Harald Surowy, Katarina Cuk, Sarah Schott, Andreas Trumpp, Klaus Pantel, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel
PURPOSE: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis. METHODS: Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients...
May 2018: Breast Cancer Research and Treatment
https://read.qxmd.com/read/29334844/the-molecular-signature-of-aml-with-increased-aldh-activity-suggests-a-stem-cell-origin
#17
Rachel Blume, Eugen Rempel, Linda Manta, Borhan R Saeed, Wenwen Wang, Simon Raffel, Olga Ermakova, Volker Eckstein, Vladimir Benes, Andreas Trumpp, Anthony D Ho, Christoph Lutz
Enrichment of leukemic blasts with a stem cell phenotype correlates with poor survival in acute myeloid leukemia (AML). In this context, measurement of the stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor prognosis cases with increased fractions of ALDH-positive cells (ALDH-numerous AML) and favorable outcome cases with low percentages (ALDH-rare AML). It has been shown that ALDH-numerous AML favor leukemic engraftment in xenotransplantation assays which suggests increased leukemic stem cell (LSC) potential...
September 2018: Leukemia & Lymphoma
https://read.qxmd.com/read/29258294/senescence-associated-reprogramming-promotes-cancer-stemness
#18
Maja Milanovic, Dorothy N Y Fan, Dimitri Belenki, J Henry M Däbritz, Zhen Zhao, Yong Yu, Jan R Dörr, Lora Dimitrova, Dido Lenze, Ines A Monteiro Barbosa, Marco A Mendoza-Parra, Tamara Kanashova, Marlen Metzner, Katharina Pardon, Maurice Reimann, Andreas Trumpp, Bernd Dörken, Johannes Zuber, Hinrich Gronemeyer, Michael Hummel, Gunnar Dittmar, Soyoung Lee, Clemens A Schmitt
Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16INK4a , p21CIP1 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells...
January 4, 2018: Nature
https://read.qxmd.com/read/29180611/screening-drug-effects-in-patient-derived-cancer-cells-links-organoid-responses-to-genome-alterations
#19
Julia Jabs, Franziska M Zickgraf, Jeongbin Park, Steve Wagner, Xiaoqi Jiang, Katharina Jechow, Kortine Kleinheinz, Umut H Toprak, Marc A Schneider, Michael Meister, Saskia Spaich, Marc Sütterlin, Matthias Schlesner, Andreas Trumpp, Martin Sprick, Roland Eils, Christian Conrad
Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced, matrix-dependent organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro , an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. Using DeathPro , we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs...
November 27, 2017: Molecular Systems Biology
https://read.qxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#20
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
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