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      WUSCHEL acts as an auxin response rheostat to maintain apical stem cells in Arabidopsis

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          Abstract

          To maintain the balance between long-term stem cell self-renewal and differentiation, dynamic signals need to be translated into spatially precise and temporally stable gene expression states. In the apical plant stem cell system, local accumulation of the small, highly mobile phytohormone auxin triggers differentiation while at the same time, pluripotent stem cells are maintained throughout the entire life-cycle. We find that stem cells are resistant to auxin mediated differentiation, but require low levels of signaling for their maintenance. We demonstrate that the WUSCHEL transcription factor confers this behavior by rheostatically controlling the auxin signaling and response pathway. Finally, we show that WUSCHEL acts via regulation of histone acetylation at target loci, including those with functions in the auxin pathway. Our results reveal an important mechanism that allows cells to differentially translate a potent and highly dynamic developmental signal into stable cell behavior with high spatial precision and temporal robustness.

          Abstract

          Spatial control of auxin signaling maintains a balance between stem-cell self-renewal and differentiation at the plant shoot apex. Here Ma et al. show that rheostatic control of auxin response by the WUSCHEL transcription factor maintains stem cells by conferring resistance to auxin mediated differentiation.

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          Most cited references42

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          The stem cell population of Arabidopsis shoot meristems in maintained by a regulatory loop between the CLAVATA and WUSCHEL genes.

          The higher-plant shoot meristem is a dynamic structure whose maintenance depends on the coordination of two antagonistic processes, organ initiation and self-renewal of the stem cell population. In Arabidopsis shoot and floral meristems, the WUSCHEL (WUS) gene is required for stem cell identity, whereas the CLAVATA1, 2, and 3 (CLV) genes promote organ initiation. Our analysis of the interactions between these key regulators indicates that (1) the CLV genes repress WUS at the transcript level and that (2) WUS expression is sufficient to induce meristem cell identity and the expression of the stem cell marker CLV3. Our data suggest that the shoot meristem has properties of a self-regulatory system in which WUS/CLV interactions establish a feedback loop between the stem cells and the underlying organizing center.
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              Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.

              (R)-Trichostatin A (TSA) is a Streptomyces product which causes the induction of Friend cell differentiation and specific inhibition of the cell cycle of normal rat fibroblasts in the G1 and G2 phases at the very low concentrations. We found that TSA caused an accumulation of acetylated histone species in a variety of mammalian cell lines. Pulse-labeling experiments indicated that TSA markedly prolonged the in vivo half-life of the labile acetyl groups on histones in mouse mammary gland tumor cells, FM3A. The partially purified histone deacetylase from wild-type FM3A cells was effectively inhibited by TSA in a noncompetitive manner with Ki = 3.4 nM. A newly isolated mutant cell line of FM3A resistant to TSA did not show the accumulation of the acetylated histones in the presence of a higher concentration of TSA. The histone deacetylase preparation from the mutant showed decreased sensitivity to TSA (Ki = 31 nM, noncompetitive). These results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme.
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                Author and article information

                Contributors
                jlohmann@meristemania.org
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                8 November 2019
                8 November 2019
                2019
                : 10
                : 5093
                Affiliations
                [1 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Department of Stem Cell Biology, Centre for Organismal Studies, , Heidelberg University, ; D-69120 Heidelberg, Germany
                [2 ]ISNI 0000 0001 2169 3852, GRID grid.4299.6, Vienna Biocenter (VBC), Gregor Mendel Institute (GMI), , Austrian Academy of Sciences, ; Dr. Bohr-Gasse 3, 1030 Vienna, Austria
                [3 ]ISNI 0000 0001 2175 9188, GRID grid.15140.31, Laboratoire Reproduction et Développement des Plantes, , University of Lyon, ENS de Lyon, ; UCB Lyon 1, CNRS, INRA, F-69342 Lyon, France
                [4 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Department of Developmental Physiology, Centre for Organismal Studies, , Heidelberg University, ; D-69120 Heidelberg, Germany
                Author information
                http://orcid.org/0000-0003-2581-672X
                http://orcid.org/0000-0002-6406-7066
                http://orcid.org/0000-0002-8257-4088
                http://orcid.org/0000-0002-6176-646X
                http://orcid.org/0000-0003-3667-187X
                Article
                13074
                10.1038/s41467-019-13074-9
                6841675
                31704928
                ac8cb5d8-bda2-4afc-982e-3ef33b6ed028
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 January 2019
                : 14 August 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000854, Human Frontier Science Program (HFSP);
                Award ID: RPG0054-2013
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001665, Agence Nationale de la Recherche (French National Research Agency);
                Award ID: ANR-12-BSV6-0005
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);
                Award ID: SFB1101
                Award ID: SFB873
                Award ID: SFB1101
                Award ID: SFB873
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                cell fate,plant stem cell,shoot apical meristem,auxin
                Uncategorized
                cell fate, plant stem cell, shoot apical meristem, auxin

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