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169 results on '"Kokkaliaris, Konstantinos D."'

1. Cranioencephalic functional lymphoid units in glioblastoma

Author

Dobersalske, Celia, Rauschenbach, Laurèl, Hua, Yichao, Berliner, Christoph, Steinbach, Anita, Grüneboom, Anika, Kokkaliaris, Konstantinos D., Heiland, Dieter H., Berger, Pia, Langer, Sarah, Tan, Chin L., Stenzel, Martin, Landolsi, Somaya, Weber, Flora, Darkwah Oppong, Marvin, Werner, Rudolf A., Gull, Hanah, Schröder, Thomas, Linsenmann, Thomas, Buck, Andreas K., Gunzer, Matthias, Stuschke, Martin, Keyvani, Kathy, Forsting, Michael, Glas, Martin, Kipnis, Jonathan, Steindler, Dennis A., Reinhardt, Hans Christian, Green, Edward W., Platten, Michael, Tasdogan, Alpaslan, Herrmann, Ken, Rambow, Florian, Cima, Igor, Sure, Ulrich, and Scheffler, Björn

Published
2024
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4. Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany

Author

Mandel, Philipp, Hoeh, Benedikt, Humke, Clara, Doering, Claudia, Wenzel, Mike, Cano Garcia, Cristina, Fuhr, Nina, Koll, Florestan, Fassl, Anne, Tilki, Derya, Steuber, Thomas, Faull, Iris, Jeroch, Jan, Ebner, Silvana, Schmitt, Christina, Reis, Henning, Köllermann, Jens, Kokkaliaris, Konstantinos D., Demes, Melanie C., Chun, Felix K.H., and Wild, Peter J.

Published
2024
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5. Live-animal imaging of native haematopoietic stem and progenitor cells

Author

Christodoulou, Constantina, Spencer, Joel A, Yeh, Shu-Chi A, Turcotte, Raphaël, Kokkaliaris, Konstantinos D, Panero, Riccardo, Ramos, Azucena, Guo, Guoji, Seyedhassantehrani, Negar, Esipova, Tatiana V, Vinogradov, Sergei A, Rudzinskas, Sarah, Zhang, Yi, Perkins, Archibald S, Orkin, Stuart H, Calogero, Raffaele A, Schroeder, Timm, Lin, Charles P, and Camargo, Fernando D

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Transplantation, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Animals, Bone Remodeling, Cell Movement, Cell Proliferation, Cell Survival, Female, Genes, Reporter, Hematopoietic Stem Cells, Hypoxia, MDS1 and EVI1 Complex Locus Protein, Male, Mice, Molecular Imaging, Oxygen, Skull, fms-Like Tyrosine Kinase 3, General Science & Technology
Abstract

The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow3-5. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.

Published
2020

6. B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis

Author

Schloss, Maximilian J., Hulsmans, Maarten, Rohde, David, Lee, I-Hsiu, Severe, Nicolas, Foy, Brody H., Pulous, Fadi E., Zhang, Shuang, Kokkaliaris, Konstantinos D., Frodermann, Vanessa, Courties, Gabriel, Yang, Chongbo, Iwamoto, Yoshiko, Knudsen, Anders Steen, McAlpine, Cameron S., Yamazoe, Masahiro, Schmidt, Stephen P., Wojtkiewicz, Gregory R., Masson, Gustavo Santos, Gustafsson, Karin, Capen, Diane, Brown, Dennis, Higgins, John M., Scadden, David T., Libby, Peter, Swirski, Filip K., Naxerova, Kamila, and Nahrendorf, Matthias

Published
2022
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9. Author Correction: B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis

Author

Schloss, Maximilian J., Hulsmans, Maarten, Rohde, David, Lee, I-Hsiu, Severe, Nicolas, Foy, Brody H., Pulous, Fadi E., Zhang, Shuang, Kokkaliaris, Konstantinos D., Frodermann, Vanessa, Courties, Gabriel, Yang, Chongbo, Iwamoto, Yoshiko, Knudsen, Anders Steen, McAlpine, Cameron S., Yamazoe, Masahiro, Schmidt, Stephen P., Wojtkiewicz, Gregory R., Masson, Gustavo Santos, Gustafsson, Karin, Capen, Diane, Brown, Dennis, Higgins, John M., Scadden, David T., Libby, Peter, Swirski, Filip K., Naxerova, Kamila, and Nahrendorf, Matthias

Published
2022
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16. Thymic mesenchymal niche cells drive T cell immune regeneration

Author

Gustafsson, Karin, primary, Isaev, Sergey, additional, Kooshesh, Kameron A., additional, Baryawno, Ninib, additional, Kokkaliaris, Konstantinos D., additional, Severe, Nicolas, additional, Zhao, Ting, additional, Scadden, Elizabeth W., additional, Spencer, Joel A., additional, Burns, Christian, additional, Akilan, Kumaran, additional, Barkas, Nikolaos, additional, Gessessew, Hayalneh, additional, Lin, Charles P., additional, Kharchenko, Peter V., additional, and Scadden, David T., additional

Published
2022
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17. The Brain Pre-Metastatic Niche: Biological and Technical Advancements.

Author

Geissler, Maximilian, Jia, Weiyi, Kiraz, Emine Nisanur, Kulacz, Ida, Liu, Xiao, Rombach, Adrian, Prinz, Vincent, Jussen, Daniel, Kokkaliaris, Konstantinos D., Medyouf, Hind, Sevenich, Lisa, Czabanka, Marcus, and Broggini, Thomas

Subjects
BRAIN metastasis, METASTASIS
Abstract

Metastasis, particularly brain metastasis, continues to puzzle researchers to this day, and exploring its molecular basis promises to break ground in developing new strategies for combatting this deadly cancer. In recent years, the research focus has shifted toward the earliest steps in the formation of metastasis. In this regard, significant progress has been achieved in understanding how the primary tumor affects distant organ sites before the arrival of tumor cells. The term pre-metastatic niche was introduced for this concept and encompasses all influences on sites of future metastases, ranging from immunological modulation and ECM remodeling to the softening of the blood–brain barrier. The mechanisms governing the spread of metastasis to the brain remain elusive. However, we begin to understand these processes by looking at the earliest steps in the formation of metastasis. This review aims to present recent findings on the brain pre-metastatic niche and to discuss existing and emerging methods to further explore the field. We begin by giving an overview of the pre-metastatic and metastatic niches in general before focusing on their manifestations in the brain. To conclude, we reflect on the methods usually employed in this field of research and discuss novel approaches in imaging and sequencing. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios

Author

Hoppe, Philipp S., Schwarzfischer, Michael, Loeffler, Dirk, Kokkaliaris, Konstantinos D., Hilsenbeck, Oliver, Moritz, Nadine, Endele, Max, Filipczyk, Adam, Gambardella, Adriana, Ahmed, Nouraiz, Etzrodt, Martin, Coutu, Daniel L., Rieger, Michael A., Marr, Carsten, Strasser, Michael K., Schauberger, Bernhard, Burtscher, Ingo, Ermakova, Olga, Burger, Antje, Lickert, Heiko, Nerlov, Claus, Theis, Fabian J., and Schroeder, Timm

Subjects
Gene expression -- Analysis, Cell populations -- Research -- Analysis, Transcription factors -- Research -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors (1,2) with the capacity for lineage reprogramming (3), positive auto-regulation (4,5) and mutual inhibition (6,7) have been described as [...]

Published
2016

20. tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche

Author

Kfoury, Youmna S., primary, Ji, Fei, additional, Mazzola, Michael, additional, Sykes, David B., additional, Scherer, Allison K., additional, Anselmo, Anthony, additional, Akiyama, Yasutoshi, additional, Mercier, Francois, additional, Severe, Nicolas, additional, Kokkaliaris, Konstantinos D., additional, Zhao, Ting, additional, Brouse, Thomas, additional, Saez, Borja, additional, Seidl, Jefferson, additional, Papazian, Ani, additional, Ivanov, Pavel, additional, Mansour, Michael K., additional, Sadreyev, Ruslan I., additional, and Scadden, David T., additional

Published
2021
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22. A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia

Author

Massachusetts Institute of Technology. Department of Biology, Baryawno, Ninib, Przybylski, Dariusz, Kowalczyk, Monika S., Kfoury, Youmna, Severe, Nicolas, Gustafsson, Karin, Kokkaliaris, Konstantinos D., Mercier, Francois, Tabaka, Marcin, Hofree, Matan, Dionne, Danielle, Papazian, Ani, Lee, Dongjun, Ashenberg, Orr, Subramanian, Ayshwarya, Vaishnav, Eeshit Dhaval, Rozenblatt-Rosen, Orit, Regev, Aviv, Scadden, David T., Massachusetts Institute of Technology. Department of Biology, Baryawno, Ninib, Przybylski, Dariusz, Kowalczyk, Monika S., Kfoury, Youmna, Severe, Nicolas, Gustafsson, Karin, Kokkaliaris, Konstantinos D., Mercier, Francois, Tabaka, Marcin, Hofree, Matan, Dionne, Danielle, Papazian, Ani, Lee, Dongjun, Ashenberg, Orr, Subramanian, Ayshwarya, Vaishnav, Eeshit Dhaval, Rozenblatt-Rosen, Orit, Regev, Aviv, and Scadden, David T.

Abstract

Stroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis, and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA sequencing (scRNA-seq) to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes spanning new fibroblastic and osteoblastic subpopulations including distinct osteoblast differentiation trajectories. Emerging acute myeloid leukemia impaired mesenchymal osteogenic differentiation and reduced regulatory molecules necessary for normal hematopoiesis. These data suggest that tissue stroma responds to malignant cells by disadvantaging normal parenchymal cells. Our taxonomy of the stromal compartment provides a comprehensive bone marrow cell census and experimental support for cancer cell crosstalk with specific stromal elements to impair normal tissue function and thereby enable emergent cancer., National Institutes of Health (Grant DK107784)

Published
2020

26. Fate Distribution and Regulatory Role of Human Mesenchymal Stromal Cells in Engineered Hematopoietic Bone Organs

Author

Bourgine, Paul E, Fritsch, Kristin, Pigeot, Sebastien, Takizawa, Hitoshi, Kunz, Leo, Kokkaliaris, Konstantinos D, Coutu, Daniel L, Manz, Markus G, Martin, Ivan, Schroeder, Timm, Bourgine, Paul E, Fritsch, Kristin, Pigeot, Sebastien, Takizawa, Hitoshi, Kunz, Leo, Kokkaliaris, Konstantinos D, Coutu, Daniel L, Manz, Markus G, Martin, Ivan, and Schroeder, Timm

Abstract

The generation of humanized ectopic ossicles (hOss) in mice has been proposed as an advanced translational and fundamental model to study the human hematopoietic system. The approach relies on the presence of human bone marrow-derived mesenchymal stromal cells (hMSCs) supporting the engraftment of transplanted human hematopoietic stem and progenitor cells (HSPCs). However, the functional distribution of hMSCs within the humanized microenvironment remains to be investigated. Here, we combined genetic tools and quantitative confocal microscopy to engineer and subsequently analyze hMSCs' fate and distribution in hOss. Implanted hMSCs reconstituted a humanized environment including osteocytes, osteoblasts, adipocytes, and stromal cells associated with vessels. By imaging full hOss, we identified rare physical interactions between hMSCs and human CD45+/CD34+/CD90+ cells, supporting a functional contact-triggered regulatory role of hMSCs. Our study highlights the importance of compiling quantitative information from humanized organs, to decode the interactions between the hematopoietic and the stromal compartments.

Published
2019

27. Stress-Induced Changes in Bone Marrow Stromal Cell Populations Revealed through Single-Cell Protein Expression Mapping

Author

Severe, Nicolas, primary, Karabacak, Nezihi Murat, additional, Gustafsson, Karin, additional, Baryawno, Ninib, additional, Courties, Gabriel, additional, Kfoury, Youmna, additional, Kokkaliaris, Konstantinos D., additional, Rhee, Catherine, additional, Lee, Dongjun, additional, Scadden, Elizabeth W., additional, Garcia-Robledo, Juan Esteban, additional, Brouse, Thomas, additional, Nahrendorf, Matthias, additional, Toner, Mehmet, additional, and Scadden, David T., additional

Published
2019
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28. A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia

Author

Baryawno, Ninib, primary, Przybylski, Dariusz, additional, Kowalczyk, Monika S., additional, Kfoury, Youmna, additional, Severe, Nicolas, additional, Gustafsson, Karin, additional, Kokkaliaris, Konstantinos D., additional, Mercier, Francois, additional, Tabaka, Marcin, additional, Hofree, Matan, additional, Dionne, Danielle, additional, Papazian, Ani, additional, Lee, Dongjun, additional, Ashenberg, Orr, additional, Subramanian, Ayshwarya, additional, Vaishnav, Eeshit Dhaval, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Scadden, David T., additional

Published
2019
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31. Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells

Author

Hastreiter, Simon, primary, Skylaki, Stavroula, additional, Loeffler, Dirk, additional, Reimann, Andreas, additional, Hilsenbeck, Oliver, additional, Hoppe, Philipp S., additional, Coutu, Daniel L., additional, Kokkaliaris, Konstantinos D., additional, Schwarzfischer, Michael, additional, Anastassiadis, Konstantinos, additional, Theis, Fabian J., additional, and Schroeder, Timm, additional

Published
2018
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34. Prospective identification of hematopoietic lineage choice by deep learning

Author

Buggenthin, Felix, primary, Buettner, Florian, additional, Hoppe, Philipp S, additional, Endele, Max, additional, Kroiss, Manuel, additional, Strasser, Michael, additional, Schwarzfischer, Michael, additional, Loeffler, Dirk, additional, Kokkaliaris, Konstantinos D, additional, Hilsenbeck, Oliver, additional, Schroeder, Timm, additional, Theis, Fabian J, additional, and Marr, Carsten, additional

Published
2017
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35. Variation in Mesenchymal KITL/SCF and IGF1 Expression at Middle Age Underlies Steady-State Hematopoietic Stem Cell Aging

Author

Young, Kira A., Telpoukhovskaia, Maria A., Hofmann, Johanna, Mistry, Jayna J., Kokkaliaris, Konstantinos D., and Trowbridge, Jennifer J.

Abstract

•Kitl and Igf1 in mesenchymal stromal cells at middle age correlates with aging-associated molecular programs in HSCs in individual mice•Elevation of pro-inflammatory cytokines is not observed in steady state middle aged mice

Published
2024
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36. Software tools for single-cell tracking and quantification of cellular and molecular properties

Author

Hilsenbeck, Oliver, primary, Schwarzfischer, Michael, additional, Skylaki, Stavroula, additional, Schauberger, Bernhard, additional, Hoppe, Philipp S, additional, Loeffler, Dirk, additional, Kokkaliaris, Konstantinos D, additional, Hastreiter, Simon, additional, Skylaki, Eleni, additional, Filipczyk, Adam, additional, Strasser, Michael, additional, Buggenthin, Felix, additional, Feigelman, Justin S, additional, Krumsiek, Jan, additional, van den Berg, Adrianus J J, additional, Endele, Max, additional, Etzrodt, Martin, additional, Marr, Carsten, additional, Theis, Fabian J, additional, and Schroeder, Timm, additional

Published
2016
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39. Network plasticity of pluripotency transcription factors in embryonic stem cells

Author

Filipczyk, Adam, primary, Marr, Carsten, additional, Hastreiter, Simon, additional, Feigelman, Justin, additional, Schwarzfischer, Michael, additional, Hoppe, Philipp S., additional, Loeffler, Dirk, additional, Kokkaliaris, Konstantinos D., additional, Endele, Max, additional, Schauberger, Bernhard, additional, Hilsenbeck, Oliver, additional, Skylaki, Stavroula, additional, Hasenauer, Jan, additional, Anastassiadis, Konstantinos, additional, Theis, Fabian J., additional, and Schroeder, Timm, additional

Published
2015
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40. CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

Author

Mende, Nicole, primary, Kuchen, Erika E, additional, Lesche, Mathias, additional, Grinenko, Tatyana, additional, Kokkaliaris, Konstantinos D, additional, Hanenberg, Helmut, additional, Lindemann, Dirk, additional, Dahl, Andreas, additional, Platz, Alexander, additional, Höfer, Thomas, additional, Calegari, Federico, additional, and Waskow, Claudia, additional

Published
2015
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41. Bloody signals: From birth to disease and death

Author

Trompouki, Eirini, primary, King, Katherine Y., additional, Will, Britta, additional, Lessard, Julie, additional, Flores-Figueroa, Eugenia, additional, Kokkaliaris, Konstantinos D., additional, and Bowman, Teresa, additional

Published
2014
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42. Multicolor quantitative confocal imaging cytometry

Author

Coutu, Daniel L, Kokkaliaris, Konstantinos D, Kunz, Leo, and Schroeder, Timm

Abstract

Multicolor 3D quantitative imaging of large tissue volumes is necessary to understand tissue development and organization as well as interactions between distinct cell types in situ. However, tissue imaging remains technically challenging, particularly imaging of bone and marrow. Here, we describe a pipeline to reproducibly generate high-dimensional quantitative data from bone and bone marrow that may be extended to any tissue. We generate thick bone sections from adult mouse femurs with preserved tissue microarchitecture and demonstrate eight-color imaging using confocal microscopy without linear unmixing. We introduce XiT, an open-access software for fast and easy data curation, exploration and quantification of large imaging data sets with single-cell resolution. We describe how XiT can be used to correct for potential artifacts in quantitative 3D imaging, and we use the pipeline to measure the spatial relationship between hematopoietic cells, bone matrix and marrow Schwann cells.

Published
2018
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43. Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Author

Swiers, Gemma, primary, Baumann, Claudia, additional, O’Rourke, John, additional, Giannoulatou, Eleni, additional, Taylor, Stephen, additional, Joshi, Anagha, additional, Moignard, Victoria, additional, Pina, Cristina, additional, Bee, Thomas, additional, Kokkaliaris, Konstantinos D., additional, Yoshimoto, Momoko, additional, Yoder, Mervin C., additional, Frampton, Jon, additional, Schroeder, Timm, additional, Enver, Tariq, additional, Göttgens, Berthold, additional, and de Bruijn, Marella F. T. R., additional

Published
2013
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44. Drosophila oogenesis as a bio-marker responding to EMF sources

Author

Margaritis, Lukas H., primary, Manta, Areti K., additional, Kokkaliaris, Konstantinos D., additional, Schiza, Dimitra, additional, Alimisis, Konstantinos, additional, Barkas, Georgios, additional, Georgiou, Eleana, additional, Giannakopoulou, Olympia, additional, Kollia, Ioanna, additional, Kontogianni, Georgia, additional, Kourouzidou, Angeliki, additional, Myari, Angeliki, additional, Roumelioti, Fani, additional, Skouroliakou, Aikaterini, additional, Sykioti, Vasia, additional, Varda, Georgia, additional, Xenos, Konstantinos, additional, and Ziomas, Konstantinos, additional

Published
2013
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47. HOXB4 Can Enhance the Differentiation of Embryonic Stem Cells by Modulating the Hematopoietic Niche

Author

Jackson, Melany, primary, Axton, Richard A., additional, Taylor, A. Helen, additional, Wilson, Julie A., additional, Gordon-Keylock, Sabrina A.M., additional, Kokkaliaris, Konstantinos D., additional, Brickman, Joshua M., additional, Schulz, Herbert, additional, Hummel, Oliver, additional, Hubner, Norbert, additional, and Forrester, Lesley M., additional

Published
2012
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48. Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios

Author

Hoppe, Philipp S., Schwarzfischer, Michael, Loeffler, Dirk, Kokkaliaris, Konstantinos D., Hilsenbeck, Oliver, Moritz, Nadine, Endele, Max, Filipczyk, Adam, Gambardella, Adriana, Ahmed, Nouraiz, Etzrodt, Martin, Coutu, Daniel L., Rieger, Michael A., Marr, Carsten, Strasser, Michael K., Schauberger, Bernhard, Burtscher, Ingo, Ermakova, Olga, Bürger, Antje, Lickert, Heiko, Nerlov, Claus, Theis, Fabian J., and Schroeder, Timm

Abstract

The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses. Alternative models of lineage choice therefore cannot be excluded. Here we use novel reporter mouse lines and live imaging for continuous single-cell long-term quantification of the transcription factors GATA1 and PU.1 (also known as SPI1). We analyse individual haematopoietic stem cells throughout differentiation into megakaryocytic–erythroid and granulocytic–monocytic lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates megakaryocytic–erythroid versus granulocytic–monocytic lineage decision-making. Rather, our findings suggest that these transcription factors are only executing and reinforcing lineage choice once made. These results challenge the current prevailing model of early myeloid lineage choice.

Published
2017
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50. Network plasticity of pluripotency transcription factors in embryonic stem cells.

Author

Hastreiter, Simon, Hoppe, Philipp S., Loeffler, Dirk, Kokkaliaris, Konstantinos D., Endele, Max, Schauberger, Bernhard, Hilsenbeck, Oliver, Skylaki, Stavroula, Hasenauer, Jan, Theis, Fabian J., Schroeder, Timm, Filipczyk, Adam, Marr, Carsten, Feigelman, Justin, Schwarzfischer, Michael, and Anastassiadis, Konstantinos

Subjects
NEUROPLASTICITY, TRANSCRIPTION factors, EMBRYONIC stem cells, GENE expression, PROTEINS
Abstract

Transcription factor (TF) networks are thought to regulate embryonic stem cell (ESC) pluripotency. However, TF expression dynamics and regulatory mechanisms are poorly understood. We use reporter mouse ESC lines allowing non-invasive quantification of Nanog or Oct4 protein levels and continuous long-term single-cell tracking and quantification over many generations to reveal diverse TF protein expression dynamics. For cells with low Nanog expression, we identified two distinct colony types: one re-expressed Nanog in a mosaic pattern, and the other did not re-express Nanog over many generations. Although both expressed pluripotency markers, they exhibited differences in their TF protein correlation networks and differentiation propensities. Sister cell analysis revealed that differences in Nanog levels are not necessarily accompanied by differences in the expression of other pluripotency factors. Thus, regulatory interactions of pluripotency TFs are less stringently implemented in individual self-renewing ESCs than assumed at present. [ABSTRACT FROM AUTHOR]

Published
2015
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