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  • 1
    Publication Date: 2013-07-23
    Description: Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle-coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913367/" 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/PMC3913367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kueh, Hao Yuan -- Champhekar, Ameya -- Nutt, Stephen L -- Elowitz, Michael B -- Rothenberg, Ellen V -- R01 AI083514/AI/NIAID NIH HHS/ -- R01 CA090233/CA/NCI NIH HHS/ -- R01 CA90233/CA/NCI NIH HHS/ -- R33 HL089123/HL/NHLBI NIH HHS/ -- RC2 CA148278/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):670-3. doi: 10.1126/science.1240831. Epub 2013 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA, USA. kueh@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23868921" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle/*genetics ; Cell Differentiation/*genetics ; Cells, Cultured ; Feedback, Physiological ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Macrophages/cytology ; Mice ; Mice, Inbred Strains ; Myeloid Cells/*cytology ; Precursor Cells, B-Lymphoid/*cytology ; Proto-Oncogene Proteins/genetics/*physiology ; Trans-Activators/genetics/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-02-15
    Description: The thymus is the nursery where T cell precursors mature into T cells of the and lineages. In a Perspective, Rothenberg discusses intriguing findings that reveal a new level of regulation in the thymus (Silva-Santos et al.). Apparently, double-positive T cells that are destined to mature into T cells directly regulate the development of the T-cell lineage through the production of lymphotoxin and the action of a transcription factor called RORt.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothenberg, Ellen V -- New York, N.Y. -- Science. 2005 Feb 11;307(5711):858-859.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15708841" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothenberg, Ellen V -- New York, N.Y. -- Science. 2005 Feb 11;307(5711):858-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. evroth@its.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15709236" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Gene Expression ; Gene Expression Regulation ; Gene Rearrangement, T-Lymphocyte ; Genes, T-Cell Receptor ; Lymph Nodes/cytology/embryology ; Lymphotoxin-alpha/biosynthesis/genetics/*physiology ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Phenotype ; Receptors, Antigen, T-Cell, alpha-beta/biosynthesis ; Receptors, Antigen, T-Cell, gamma-delta/biosynthesis ; Receptors, Retinoic Acid/genetics/*physiology ; Receptors, Thyroid Hormone/genetics/*physiology ; T-Lymphocyte Subsets/cytology/*immunology/*physiology ; Thymus Gland/cytology/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothenberg, E V -- New York, N.Y. -- Science. 1996 Jul 5;273(5271):78-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658200" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen-Presenting Cells/immunology ; Antigens/immunology ; Antigens, CD28/immunology ; Down-Regulation ; Humans ; Ligands ; *Lymphocyte Activation ; Receptors, Antigen, T-Cell/*immunology ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2010-07-03
    Description: The identities of the regulators that mediate commitment of hematopoietic precursors to the T lymphocyte lineage have been unknown. The last stage of T lineage commitment in vivo involves mechanisms to suppress natural killer cell potential, to suppress myeloid and dendritic cell potential, and to silence the stem cell or progenitor cell regulatory functions that initially provide T cell receptor-independent self-renewal capability. The zinc finger transcription factor Bcl11b is T cell-specific in expression among hematopoietic cell types and is first expressed in precursors immediately before T lineage commitment. We found that Bcl11b is necessary for T lineage commitment in mice and is specifically required both to repress natural killer cell-associated genes and to down-regulate a battery of stem cell or progenitor cell genes at the pivotal stage of commitment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935300/" 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/PMC2935300/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Long -- Leid, Mark -- Rothenberg, Ellen V -- F06 TW002367/TW/FIC NIH HHS/ -- F06 TW002367-01A1/TW/FIC NIH HHS/ -- R01 GM060852/GM/NIGMS NIH HHS/ -- R01 GM060852-04/GM/NIGMS NIH HHS/ -- R01 GM60852/GM/NIGMS NIH HHS/ -- R33 HL089123/HL/NHLBI NIH HHS/ -- R33 HL089123-03/HL/NHLBI NIH HHS/ -- RC2 CA148278/CA/NCI NIH HHS/ -- RC2 CA148278-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):89-93. doi: 10.1126/science.1188989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595614" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; *Cell Lineage ; Cells, Cultured ; Down-Regulation ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genes, T-Cell Receptor delta ; Genes, T-Cell Receptor gamma ; Killer Cells, Natural/cytology/physiology ; *Lymphopoiesis/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Precursor Cells, T-Lymphoid/cytology/immunology/*physiology ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Receptors, Notch/metabolism ; Repressor Proteins/deficiency/genetics/*metabolism ; Signal Transduction ; T-Lymphocytes/cytology/metabolism/*physiology ; Transcription Factors/genetics/metabolism ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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