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  • 1
    Publication Date: 2010-02-16
    Description: A major goal of regenerative medicine is to instruct formation of multipotent, tissue-specific stem cells from induced pluripotent stem cells (iPSCs) for cell replacement therapies. Generation of haematopoietic stem cells (HSCs) from iPSCs or embryonic stem cells (ESCs) is not currently possible, however, necessitating a better understanding of how HSCs normally arise during embryonic development. We previously showed that haematopoiesis occurs through four distinct waves during zebrafish development, with HSCs arising in the final wave in close association with the dorsal aorta. Recent reports have suggested that murine HSCs derive from haemogenic endothelial cells (ECs) lining the aortic floor. Additional in vitro studies have similarly indicated that the haematopoietic progeny of ESCs arise through intermediates with endothelial potential. Here we have used the unique strengths of the zebrafish embryo to image directly the generation of HSCs from the ventral wall of the dorsal aorta. Using combinations of fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry, we have identified and isolated the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. Finally, using a permanent lineage tracing strategy, we demonstrate that the HSCs generated from haemogenic endothelium are the lineal founders of the adult haematopoietic system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858358/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858358/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bertrand, Julien Y -- Chi, Neil C -- Santoso, Buyung -- Teng, Shutian -- Stainier, Didier Y R -- Traver, David -- DK074482/DK/NIDDK NIH HHS/ -- F32DK752433/DK/NIDDK NIH HHS/ -- HL074891/HL/NHLBI NIH HHS/ -- HL54737/HL/NHLBI NIH HHS/ -- R01 DK074482/DK/NIDDK NIH HHS/ -- R01 DK074482-04/DK/NIDDK NIH HHS/ -- England -- Nature. 2010 Mar 4;464(7285):108-11. doi: 10.1038/nature08738. Epub 2010 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20154733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Aorta/*cytology/*embryology ; *Cell Differentiation ; *Cell Lineage ; Cell Separation ; Endothelial Cells/cytology ; Endothelium, Vascular/*cytology/embryology ; Female ; Flow Cytometry ; Genes, Reporter/genetics ; Hematopoietic Stem Cells/*cytology ; Male ; Microscopy, Confocal ; Microscopy, Fluorescence ; Transgenes/genetics ; Zebrafish/blood/*embryology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-06-21
    Description: Despite current treatment regimens, heart failure remains the leading cause of morbidity and mortality in the developed world due to the limited capacity of adult mammalian ventricular cardiomyocytes to divide and replace ventricular myocardium lost from ischaemia-induced infarct. Hence there is great interest to identify potential cellular sources and strategies to generate new ventricular myocardium. Past studies have shown that fish and amphibians and early postnatal mammalian ventricular cardiomyocytes can proliferate to help regenerate injured ventricles; however, recent studies have suggested that additional endogenous cellular sources may contribute to this overall ventricular regeneration. Here we have developed, in the zebrafish (Danio rerio), a combination of fluorescent reporter transgenes, genetic fate-mapping strategies and a ventricle-specific genetic ablation system to discover that differentiated atrial cardiomyocytes can transdifferentiate into ventricular cardiomyocytes to contribute to zebrafish cardiac ventricular regeneration. Using in vivo time-lapse and confocal imaging, we monitored the dynamic cellular events during atrial-to-ventricular cardiomyocyte transdifferentiation to define intermediate cardiac reprogramming stages. We observed that Notch signalling becomes activated in the atrial endocardium following ventricular ablation, and discovered that inhibiting Notch signalling blocked the atrial-to-ventricular transdifferentiation and cardiac regeneration. Overall, these studies not only provide evidence for the plasticity of cardiac lineages during myocardial injury, but more importantly reveal an abundant new potential cardiac resident cellular source for cardiac ventricular regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090927/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ruilin -- Han, Peidong -- Yang, Hongbo -- Ouyang, Kunfu -- Lee, Derek -- Lin, Yi-Fan -- Ocorr, Karen -- Kang, Guson -- Chen, Ju -- Stainier, Didier Y R -- Yelon, Deborah -- Chi, Neil C -- DP2 OD007464/OD/NIH HHS/ -- HL104239/HL/NHLBI NIH HHS/ -- HL54737/HL/NHLBI NIH HHS/ -- OD007464/OD/NIH HHS/ -- R01 HD069305/HD/NICHD NIH HHS/ -- R01 HL054737/HL/NHLBI NIH HHS/ -- R01 HL069594/HL/NHLBI NIH HHS/ -- R01 HL104239/HL/NHLBI NIH HHS/ -- R01 HL108599/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 Jun 27;498(7455):497-501. doi: 10.1038/nature12322. Epub 2013 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23783515" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death ; *Cell Transdifferentiation ; *Cellular Reprogramming ; Heart/embryology/*physiology ; Heart Atria/cytology/embryology ; Heart Ventricles/cytology ; Myocardium/*cytology/metabolism ; Myocytes, Cardiac/cytology/metabolism ; Receptor, Notch1/metabolism ; Regeneration/*physiology ; Signal Transduction ; Zebrafish/embryology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-02-20
    Description: Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leung, Danny -- Jung, Inkyung -- Rajagopal, Nisha -- Schmitt, Anthony -- Selvaraj, Siddarth -- Lee, Ah Young -- Yen, Chia-An -- Lin, Shin -- Lin, Yiing -- Qiu, Yunjiang -- Xie, Wei -- Yue, Feng -- Hariharan, Manoj -- Ray, Pradipta -- Kuan, Samantha -- Edsall, Lee -- Yang, Hongbo -- Chi, Neil C -- Zhang, Michael Q -- Ecker, Joseph R -- Ren, Bing -- ES017166/ES/NIEHS NIH HHS/ -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):350-4. doi: 10.1038/nature14217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, La Jolla, California 92093, USA. ; 1] Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA [2] Department of Cardiovascular Medicine, Stanford University, Falk Building, 870 Quarry Road Stanford, California 94304, USA. ; 1] Department of Genetics, Stanford University, 300 Pasteur Drive, M-344 Stanford, California 94305, USA [2] Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8109, St Louis, Missouri 63110, USA. ; Tsinghua University-Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; Department of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA. ; Genomic Analysis Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92093, USA. ; Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080, USA. ; Department of Medicine, Division of Cardiology, University of California, San Diego, California 92093-0613, USA. ; 1] Department of Medicine, Division of Cardiology, University of California, San Diego, California 92093-0613, USA [2] Institute of Genomic Medicine, University of California, San Diego, California 92093, USA. ; 1] Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080, USA [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing 100084, China. ; 1] Ludwig Institute for Cancer Research, La Jolla, California 92093, USA [2] Institute of Genomic Medicine, University of California, San Diego, California 92093, USA [3] Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA [4] UCSD Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693566" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; *Alleles ; Chromatin/genetics/metabolism ; Chromosomes, Human/genetics ; Datasets as Topic ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Genetic Variation/genetics ; Haplotypes/*genetics ; Histones/metabolism ; Humans ; Nucleotide Motifs ; Organ Specificity/genetics ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-07-30
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
  • 6
    Publication Date: 2011-08-18
    Description: Rapid electrical conduction in the His–Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His–Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction–forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2007-06-25
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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