122 results found
Ferreirós-Vidal I, Carroll T, Zhang T, et al., 2019, Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation., PLoS Biol, Vol: 17
The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.
Millership SJ, Tunster SJ, Van de Pette M, et al., 2018, Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice, MOLECULAR METABOLISM, Vol: 18, Pages: 97-106, ISSN: 2212-8778
Cuartero S, Weiss FD, Dharmalingam G, et al., 2018, Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation, NATURE IMMUNOLOGY, Vol: 19, Pages: 932-+, ISSN: 1529-2908
Fisher CL, Marks H, Cho LT-Y, et al., 2017, An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers, NUCLEIC ACIDS RESEARCH, Vol: 45, ISSN: 0305-1048
Cantone I, Fisher AG, 2017, Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 372, ISSN: 0962-8436
Fisher AG, Stumpf MPH, Merkenschlager M, 2017, Reconciling Epigenetic Memory and Transcriptional Responsiveness, CELL SYSTEMS, Vol: 4, Pages: 373-374, ISSN: 2405-4712
Liang Z, Brown KE, Carroll T, et al., 2017, A high-resolution map of transcriptional repression, ELIFE, Vol: 6, ISSN: 2050-084X
Van de Pette M, Abbas A, Feytout A, et al., 2017, Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults, CELL REPORTS, Vol: 18, Pages: 1090-1099, ISSN: 2211-1247
Cantone I, Dharmalingam G, Chan Y-W, et al., 2017, Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation, GENOME BIOLOGY, Vol: 18, ISSN: 1474-760X
Cantone I, Bagci H, Dormann D, et al., 2016, Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723
Graham B, Marcais A, Dharmalingam G, et al., 2016, MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells, STEM CELL REPORTS, Vol: 6, Pages: 635-642, ISSN: 2213-6711
Cellular fusion is a key process in many fields ranging from historical gene mapping studies and monoclonal antibody production, through to cell reprogramming. Traditional methodologies for cell fusion rely on the random pairing of different cell types and generally result in low and variable fusion efficiencies. These approaches become particularly limiting where substantial numbers of bespoke one-to-one fusions are required, for example, for in-depth studies of nuclear reprogramming mechanisms. In recent years, microfluidic technologies have proven valuable in creating platforms where the manipulation of single cells is highly efficient, rapid and controllable. These technologies also allow the integration of different experimental steps and characterisation processes into a single platform. Although the application of microfluidic methodologies to cell fusion studies is promising, current technologies that rely on static trapping are limited both in terms of the overall number of fused cells produced and their experimental accessibility. Here we review some of the most exciting breakthroughs in core microfluidic technologies that will allow the creation of integrated platforms for controlled cell fusion at high throughput. © 2015 Society of Chemical Industry.
Malinowski AR, Fisher AG, 2016, Reprogramming of Somatic Cells Towards Pluripotency by Cell Fusion., Pages: 289-299
Pluripotent reprogramming can be dominantly induced in a somatic nucleus upon fusion with a pluripotent cell such as embryonic stem (ES) cell. Cell fusion between ES cells and somatic cells results in the formation of heterokaryons, in which the somatic nuclei begin to acquire features of the pluripotent partner. The generation of interspecies heterokaryons between mouse ES- and human somatic cells allows an experimenter to distinguish the nuclear events occurring specifically within the reprogrammed nucleus. Therefore, cell fusion provides a simple and rapid approach to look at the early nuclear events underlying pluripotent reprogramming. Here, we describe a polyethylene glycol (PEG)-mediated cell fusion protocol to generate interspecies heterokaryons and intraspecies hybrids between ES cells and B lymphocytes or fibroblasts.
Landeira D, Bagci H, Malinowski AR, et al., 2015, Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development, CELL REPORTS, Vol: 12, Pages: 573-586, ISSN: 2211-1247
Ing-Simmons E, Seitan VC, Faure AJ, et al., 2015, Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin, GENOME RESEARCH, Vol: 25, Pages: 504-513, ISSN: 1088-9051
Blevins R, Bruno L, Carroll T, et al., 2015, microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes, PLOS GENETICS, Vol: 11, ISSN: 1553-7390
Lavagnolli T, Gupta P, Hörmanseder E, et al., 2015, Initiation and maintenance of pluripotency gene expression in the absence of cohesin., Genes Dev, Vol: 29, Pages: 23-38
Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin's contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells, which promoted DNA replication-dependent reprogramming of somatic fusion partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in heterokaryons, due in part to defective DNA replication. Pluripotency gene induction was rescued by Myc, which restored DNA replication, and by nuclear transfer, where reprogramming does not require DNA replication. These results redefine cohesin's role in pluripotency and reveal a novel function for Myc in promoting the replication-dependent reprogramming of somatic nuclei.
Marcais A, Blevins R, Graumann J, et al., 2014, microRNA-mediated regulation of mTOR complex components facilitates discrimination between activation and anergy in CD4 T cells, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 211, Pages: 2281-2295, ISSN: 0022-1007
Piccolo FM, Fisher AG, 2014, Getting rid of DNA methylation, TRENDS IN CELL BIOLOGY, Vol: 24, Pages: 136-143, ISSN: 0962-8924
Seitan VC, Faure AJ, Zhan Y, et al., 2013, Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments, GENOME RESEARCH, Vol: 23, Pages: 2066-2077, ISSN: 1088-9051
Brown KE, Bagci H, Soza-Ried J, et al., 2013, Atypical heterochromatin organization and replication are rapidly acquired by somatic cells following fusion-mediated reprogramming by mouse ESCs, CELL CYCLE, Vol: 12, Pages: 3253-3261, ISSN: 1538-4101
Bagci H, Fisher AG, 2013, DNA Demethylation in Pluripotency and Reprogramming: The Role of Tet Proteins and Cell Division, CELL STEM CELL, Vol: 13, Pages: 265-269, ISSN: 1934-5909
Piccolo FM, Bagci H, Brown KE, et al., 2013, Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion, MOLECULAR CELL, Vol: 49, Pages: 1023-1033, ISSN: 1097-2765
Piccolo FM, Bagci H, Brown KE, et al., 2013, Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion (vol 49, pg 1023, 2013), MOLECULAR CELL, Vol: 49, Pages: 1176-1176, ISSN: 1097-2765
Ferreiros-Vidal I, Carroll T, Taylor B, et al., 2013, Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation, BLOOD, Vol: 121, Pages: 1769-1782, ISSN: 0006-4971
Cantone I, Fisher AG, 2013, Epigenetic programming and reprogramming during development, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 20, Pages: 282-289, ISSN: 1545-9993
Tsubouchi T, Soza-Ried J, Brown K, et al., 2013, DNA Synthesis Is Required for Reprogramming Mediated by Stem Cell Fusion, CELL, Vol: 152, Pages: 873-883, ISSN: 0092-8674
Tsubouchi T, Fisher AG, 2013, Reprogramming and the Pluripotent Stem Cell Cycle, EPIGENETICS AND DEVELOPMENT, Editors: Heard, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 223-241, ISBN: 978-0-12-416027-9
Fisher AG, Brockdorff N, 2012, Epigenetic memory and parliamentary privilege combine to evoke discussions on inheritance, DEVELOPMENT, Vol: 139, Pages: 3891-3896, ISSN: 0950-1991
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