دورية أكاديمية
أعرض في EDS

Acly Deficiency Enhances Myelopoiesis through Acetyl Coenzyme A and Metabolic-Epigenetic Cross-Talk.

التفاصيل البيبلوغرافية
العنوان: Acly Deficiency Enhances Myelopoiesis through Acetyl Coenzyme A and Metabolic-Epigenetic Cross-Talk.
المؤلفون: Greenwood DL; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Ramsey HE; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Nguyen PTT; Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Neuroscience Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Patterson AR; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Voss K; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Bader JE; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Sugiura A; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Bacigalupa ZA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Schaefer S; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Ye X; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Dahunsi DO; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Madden MZ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN., Wellen KE; Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Savona MR; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; and.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN., Ferrell PB; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; and.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN., Rathmell JC; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; and.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN.
المصدر: ImmunoHorizons [Immunohorizons] 2022 Dec 01; Vol. 6 (12), pp. 837-850.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association of Immunologists, Inc Country of Publication: United States NLM ID: 101708159 Publication Model: Print Cited Medium: Internet ISSN: 2573-7732 (Electronic) Linking ISSN: 25737732 NLM ISO Abbreviation: Immunohorizons Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Rockville, Maryland : American Association of Immunologists, Inc., [2017]-
مواضيع طبية MeSH: ATP Citrate (pro-S)-Lyase*/deficiency , ATP Citrate (pro-S)-Lyase*/genetics , Epigenesis, Genetic* , Myelopoiesis*/genetics , Chromatin Assembly and Disassembly*, Animals ; Mice ; Acetyl Coenzyme A/genetics ; Acetyl Coenzyme A/metabolism ; Chromatin/metabolism
مستخلص: Hematopoiesis integrates cytokine signaling, metabolism, and epigenetic modifications to regulate blood cell generation. These processes are linked, as metabolites provide essential substrates for epigenetic marks. In this study, we demonstrate that ATP citrate lyase (Acly), which metabolizes citrate to generate cytosolic acetyl-CoA and is of clinical interest, can regulate chromatin accessibility to limit myeloid differentiation. Acly was tested for a role in murine hematopoiesis by small-molecule inhibition or genetic deletion in lineage-depleted, c-Kit-enriched hematopoietic stem and progenitor cells from Mus musculus. Treatments increased the abundance of cell populations that expressed the myeloid integrin CD11b and other markers of myeloid differentiation. When single-cell RNA sequencing was performed, we found that Acly inhibitor-treated hematopoietic stem and progenitor cells exhibited greater gene expression signatures for macrophages and enrichment of these populations. Similarly, the single-cell assay for transposase-accessible chromatin sequencing showed increased chromatin accessibility at genes associated with myeloid differentiation, including CD11b, CD11c, and IRF8. Mechanistically, Acly deficiency altered chromatin accessibility and expression of multiple C/EBP family transcription factors known to regulate myeloid differentiation and cell metabolism, with increased Cebpe and decreased Cebpa and Cebpb. This effect of Acly deficiency was accompanied by altered mitochondrial metabolism with decreased mitochondrial polarization but increased mitochondrial content and production of reactive oxygen species. The bias to myeloid differentiation appeared due to insufficient generation of acetyl-CoA, as exogenous acetate to support alternate compensatory pathways to produce acetyl-CoA reversed this phenotype. Acly inhibition thus can promote myelopoiesis through deprivation of acetyl-CoA and altered histone acetylome to regulate C/EBP transcription factor family activity for myeloid differentiation.
(Copyright © 2022 The Authors.)
References: Cell Rep. 2016 Oct 18;17(4):1037-1052. (PMID: 27760311)
J Cell Physiol. 1965 Dec;66(3):319-24. (PMID: 5884359)
Sci Rep. 2019 Jun 4;9(1):8262. (PMID: 31164666)
J Vis Exp. 2010 Dec 18;(46):. (PMID: 21252854)
Exp Hematol. 2019 Feb;70:70-84.e6. (PMID: 30553776)
Bioinformatics. 2017 Apr 15;33(8):1179-1186. (PMID: 28088763)
Cytotherapy. 2019 Aug;21(8):820-823. (PMID: 31257121)
Cell Biosci. 2014 May 07;4:25. (PMID: 24904742)
EMBO J. 2022 Apr 19;41(8):e109463. (PMID: 35229328)
Nat Cell Biol. 2013 Mar;15(3):309-16. (PMID: 23434824)
Cell Mol Immunol. 2021 Mar;18(3):711-722. (PMID: 32728200)
J Immunol. 2018 Jul 15;201(2):635-651. (PMID: 29907708)
Biochem J. 1998 Aug 15;334 ( Pt 1):113-9. (PMID: 9693110)
Am J Physiol Gastrointest Liver Physiol. 2020 Aug 1;319(2):G189-G196. (PMID: 32628072)
Nature. 2017 Mar 9;543(7644):205-210. (PMID: 28241143)
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Nov;1866(11):159018. (PMID: 34332074)
Curr Opin Cell Biol. 2015 Apr;33:125-31. (PMID: 25703630)
Blood Adv. 2021 Dec 14;5(23):5002-5015. (PMID: 34581809)
Nat Immunol. 2019 Feb;20(2):163-172. (PMID: 30643263)
Cytometry A. 2021 Aug;99(8):825-831. (PMID: 33325591)
PLoS Comput Biol. 2013;9(8):e1003118. (PMID: 23950696)
Front Immunol. 2021 Apr 07;12:649572. (PMID: 33897697)
Nat Genet. 2021 Mar;53(3):403-411. (PMID: 33633365)
Life Sci. 2019 Dec 15;239:116897. (PMID: 31644894)
Stem Cell Res. 2021 Aug;55:102477. (PMID: 34343826)
Blood. 2003 Apr 15;101(8):3265-73. (PMID: 12515729)
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9499-E9506. (PMID: 30228117)
J Bone Miner Res. 2021 Oct;36(10):2065-2080. (PMID: 34155695)
Nat Cell Biol. 2017 Nov;19(11):1298-1306. (PMID: 29058720)
Blood Cells Mol Dis. 2019 May;76:82-90. (PMID: 30853332)
Blood. 1982 Aug;60(2):352-61. (PMID: 7093523)
Exp Hematol. 2018 Aug;64:1-11. (PMID: 29807063)
Front Aging. 2021 Sep 27;2:738512. (PMID: 35822052)
Aust J Exp Biol Med Sci. 1966 Jun;44(3):287-99. (PMID: 4164182)
J Clin Endocrinol Metab. 2008 Dec;93(12):4880-6. (PMID: 18765514)
Cold Spring Harb Protoc. 2015 Sep 01;2015(9):pdb.prot086298. (PMID: 26330624)
Mol Cell Pharmacol. 2010;2(3):101-110. (PMID: 20686672)
J Biol Chem. 1959 Oct;234:2544-7. (PMID: 13833535)
Genome Biol. 2019 Dec 23;20(1):296. (PMID: 31870423)
J Cell Mol Med. 2005 Jan-Mar;9(1):103-12. (PMID: 15784168)
Dev Cell. 2020 Jul 20;54(2):239-255. (PMID: 32693057)
J Immunol. 2017 Mar 1;198(5):2070-2081. (PMID: 28093525)
Cell Immunol. 2017 Jun;316:53-60. (PMID: 28433199)
J Biol Chem. 1987 Apr 25;262(12):5576-80. (PMID: 3553180)
Eur J Med Genet. 2018 Feb;61(2):114-118. (PMID: 29079547)
Blood. 1976 Sep;48(3):407-17. (PMID: 953362)
Nat Commun. 2020 Dec 8;11(1):6296. (PMID: 33293558)
Biol Pharm Bull. 2020;43(12):1876-1883. (PMID: 33268705)
Blood. 1995 Jan 15;85(2):319-29. (PMID: 7811988)
J Biol Chem. 1996 Feb 16;271(7):3891-6. (PMID: 8632009)
Methods Mol Biol. 2005;290:71-89. (PMID: 15361656)
Exp Hematol. 2020 Apr;84:19-28.e4. (PMID: 32151553)
Am J Pathol. 1994 Feb;144(2):321-8. (PMID: 7508684)
Nat Commun. 2020 Mar 16;11(1):1406. (PMID: 32179749)
Nat Immunol. 2008 Oct;9(10):1091-4. (PMID: 18800157)
Nat Commun. 2018 Dec 19;9(1):5379. (PMID: 30568188)
Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118)
Cell Stem Cell. 2009 Oct 2;5(4):442-9. (PMID: 19796624)
Front Immunol. 2019 Jul 31;10:1804. (PMID: 31417568)
J Transl Med. 2019 May 10;17(1):149. (PMID: 31077215)
Blood. 2019 Jun 6;133(23):2507-2517. (PMID: 30952671)
Front Oncol. 2021 Mar 17;11:642229. (PMID: 33816292)
Front Oncol. 2015 May 26;5:108. (PMID: 26075180)
Nature. 2020 Jun;582(7810):109-114. (PMID: 32494068)
Nat Biotechnol. 2015 May;33(5):495-502. (PMID: 25867923)
Immunity. 2016 Jun 21;44(6):1312-24. (PMID: 27212436)
معلومات مُعتمدة: F31 HL152529 United States HL NHLBI NIH HHS; K00 CA234920 United States CA NCI NIH HHS; R01 AI153167 United States AI NIAID NIH HHS; R01 DK116005 United States DK NIDDK NIH HHS; R01 DK105550 United States DK NIDDK NIH HHS; T32 DK101003 United States DK NIDDK NIH HHS; F30 CA239367 United States CA NCI NIH HHS; T32 GM007347 United States GM NIGMS NIH HHS; K23 HL138291 United States HL NHLBI NIH HHS; R01 CA217987 United States CA NCI NIH HHS
المشرفين على المادة: 72-89-9 (Acetyl Coenzyme A)
EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase)
0 (Chromatin)
تواريخ الأحداث: Date Created: 20221222 Date Completed: 20230111 Latest Revision: 20231202
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9935084
DOI: 10.4049/immunohorizons.2200086
PMID: 36547387
قاعدة البيانات: MEDLINE
الوصف
تدمد:2573-7732
DOI:10.4049/immunohorizons.2200086