Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function.

Tytuł:: Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function.
Autorzy:: Eraslan G; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Drokhlyansky E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anand S; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Fiskin E; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Subramanian A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Slyper M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wang J; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Van Wittenberghe N; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rouhana JM; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Waldman J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashenberg O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lek M; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Dionne D; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Win TS; Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Cuoco MS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kuksenko O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tsankov AM; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Branton PA; The Joint Pathology Center Gynecologic/Breast Pathology, Silver Spring, MD 20910, USA.
Marshall JL; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Greka A; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Getz G; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Center for Cancer Research and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.; Harvard Medical School, Boston, MA 02115, USA.
Segrè AV; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aguet F; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ardlie KG; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Źródło:: Science (New York, N.Y.) [Science] 2022 May 13; Vol. 376 (6594), pp. eabl4290. Date of Electronic Publication: 2022 May 13.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
MeSH Terms:: Cell Nucleus*/genetics
Disease*/genetics
RNA-Seq*/methods
Biomarkers ; Genome-Wide Association Study ; Humans ; Organ Specificity ; Phenotype
References:: Nat Med. 2021 Mar;27(3):546-559. (PMID: 33654293)
Muscle Nerve. 2011 Sep;44(3):318-31. (PMID: 21949456)
Immunity. 2018 Aug 21;49(2):326-341.e7. (PMID: 30054204)
Nature. 2020 Nov;587(7835):619-625. (PMID: 33208946)
Nucleic Acids Res. 2021 Jan 8;49(D1):D1311-D1320. (PMID: 33045747)
Front Immunol. 2018 Feb 01;9:93. (PMID: 29449841)
J Biol Chem. 2008 Feb 29;283(9):5899-907. (PMID: 18083704)
Nature. 2020 Nov;587(7832):98-102. (PMID: 33116305)
Dis Markers. 2013;35(6):633-40. (PMID: 24288432)
Nat Commun. 2019 Jun 27;10(1):2832. (PMID: 31249312)
Arch Endocrinol Metab. 2021 May 18;64(5):521-527. (PMID: 34033291)
Front Physiol. 2020 Mar 19;11:253. (PMID: 32265741)
Cell. 2017 Jun 15;169(7):1276-1290.e17. (PMID: 28602351)
Nature. 2018 Nov;563(7731):347-353. (PMID: 30429548)
Cell. 2021 Jul 22;184(15):3852-3872. (PMID: 34297930)
PLoS Genet. 2017 Mar 1;13(3):e1006643. (PMID: 28248954)
Nat Immunol. 2021 Jul;22(7):839-850. (PMID: 34168371)
Front Genet. 2020 May 13;11:424. (PMID: 32477401)
Nat Med. 2019 Aug;25(8):1280-1289. (PMID: 31359001)
Sci Data. 2020 Jan 2;7(1):4. (PMID: 31896769)
Nat Commun. 2019 Jun 3;10(1):2430. (PMID: 31160583)
Cell. 2020 Sep 17;182(6):1606-1622.e23. (PMID: 32888429)
Chem Phys Lipids. 2017 Oct;207(Pt B):246-252. (PMID: 28528274)
Circ Res. 2018 Jun 8;122(12):1661-1674. (PMID: 29545365)
Nat Biotechnol. 2022 Mar;40(3):374-381. (PMID: 34675424)
Am J Hum Genet. 2016 Nov 3;99(5):1206-1216. (PMID: 27843126)
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13818-23. (PMID: 11087833)
Annu Rev Immunol. 2015;33:643-75. (PMID: 25861979)
Cell. 2020 Nov 12;183(4):1103-1116.e20. (PMID: 33098772)
Nat Genet. 2023 Aug;55(8):1267-1276. (PMID: 37443254)
Nat Genet. 2018 Jun;50(6):825-833. (PMID: 29785013)
Am J Hum Genet. 2007 Sep;81(3):589-95. (PMID: 17701904)
Nature. 2023 Jul;619(7970):585-594. (PMID: 37468583)
Immunity. 2015 Aug 18;43(2):369-81. (PMID: 26231115)
Handb Clin Neurol. 2016;133:447-66. (PMID: 27112691)
J Cell Biol. 2001 Jul 23;154(2):447-58. (PMID: 11470831)
Muscle Nerve. 2000 Apr;23(4):529-37. (PMID: 10716763)
Nature. 2019 Jun;570(7761):332-337. (PMID: 31042697)
Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17832-17841. (PMID: 32661178)
Nat Rev Neurol. 2011 Jun 21;7(7):379-90. (PMID: 21691338)
Immunity. 2020 Oct 13;53(4):878-894.e7. (PMID: 33053333)
Nat Med. 2020 May;26(5):792-802. (PMID: 32405060)
Science. 2017 Apr 21;356(6335):. (PMID: 28428369)
Science. 2017 Oct 6;358(6359):69-75. (PMID: 28983045)
J Neurosci. 2015 Apr 22;35(16):6532-43. (PMID: 25904803)
Sci Rep. 2018 Sep 11;8(1):13624. (PMID: 30206270)
Nat Neurosci. 2019 Dec;22(12):2087-2097. (PMID: 31768052)
Genome Biol. 2020 Jun 2;21(1):130. (PMID: 32487174)
Gut. 2019 Mar;68(3):533-546. (PMID: 29374630)
Nat Rev Dis Primers. 2021 Feb 18;7(1):13. (PMID: 33602943)
Immunol Rev. 2012 Sep;249(1):72-83. (PMID: 22889216)
Nature. 2019 Nov;575(7783):512-518. (PMID: 31597160)
Semin Pediatr Neurol. 2011 Dec;18(4):264-71. (PMID: 22172422)
J Biol Chem. 2005 Mar 18;280(11):10350-6. (PMID: 15623520)
Science. 2020 Sep 11;369(6509):1318-1330. (PMID: 32913098)
Neuromuscul Disord. 2020 Dec;30(12):1008-1048. (PMID: 33257164)
Am J Hum Genet. 2019 Mar 7;104(3):466-483. (PMID: 30827497)
N Engl J Med. 2001 Jan 4;344(1):30-7. (PMID: 11136958)
Int J Mol Sci. 2020 Aug 11;21(16):. (PMID: 32796696)
Science. 2016 Aug 26;353(6302):925-8. (PMID: 27471252)
Nat Commun. 2020 Feb 10;11(1):810. (PMID: 32041960)
Mol Ther Oncolytics. 2021 May 08;21:183-206. (PMID: 34027052)
Skelet Muscle. 2020 Jul 6;10(1):19. (PMID: 32624006)
J Allergy Clin Immunol. 2020 Nov;146(5):1056-1069. (PMID: 32344053)
Nature. 2002 Aug 15;418(6899):797-801. (PMID: 12181572)
PLoS Genet. 2010 Apr 15;6(4):e1000907. (PMID: 20419147)
Nature. 2017 Jan 12;541(7636):176-181. (PMID: 28002412)
Eur J Hum Genet. 2014 Jun;22(6):801-8. (PMID: 24193343)
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11981-6. (PMID: 16880404)
Reprod Med Biol. 2015 Oct 14;15(2):77-94. (PMID: 29259424)
Front Immunol. 2021 Feb 24;12:630892. (PMID: 33717163)
Nat Genet. 2018 Apr;50(4):493-497. (PMID: 29610479)
Biochem J. 2020 Mar 13;477(5):985-1008. (PMID: 32168372)
Nature. 2008 Jul 24;454(7203):445-54. (PMID: 18650915)
Mol Cell Pediatr. 2020 Oct 1;7(1):13. (PMID: 33000355)
Basic Res Cardiol. 2021 Apr 19;116(1):26. (PMID: 33876316)
Nature. 2017 Oct 11;550(7675):204-213. (PMID: 29022597)
Cell. 1997 Mar 7;88(5):603-13. (PMID: 9054500)
Sci Transl Med. 2017 Apr 19;9(386):. (PMID: 28424332)
Science. 2022 May 13;376(6594):eabl4290. (PMID: 35549429)
Nat Commun. 2020 Dec 11;11(1):6374. (PMID: 33311464)
Cell. 2020 Jun 11;181(6):1207-1217. (PMID: 32531244)
Nature. 2018 Aug;560(7718):377-381. (PMID: 30069046)
Cell. 2022 Jan 20;185(2):379-396.e38. (PMID: 35021063)
J Biol Chem. 2013 May 17;288(20):14147-14157. (PMID: 23558685)
Development. 2007 Jul;134(13):2501-9. (PMID: 17537792)
Nat Genet. 2017 Jan;49(1):139-145. (PMID: 27918533)
Cells. 2020 Jan 28;9(2):. (PMID: 32013057)
Pflugers Arch. 2021 Dec;473(12):1813-1839. (PMID: 34553265)
Front Endocrinol (Lausanne). 2022 Jan 03;12:803189. (PMID: 35046902)
Curr Opin Neurol. 2019 Oct;32(5):696-703. (PMID: 31361628)
Nat Genet. 2018 Jul;50(7):956-967. (PMID: 29955180)
Nat Genet. 2015 Nov;47(11):1228-35. (PMID: 26414678)
Nat Methods. 2017 Oct;14(10):955-958. (PMID: 28846088)
Nat Cell Biol. 2020 Dec;22(12):1436-1446. (PMID: 33257808)
Exerc Sport Sci Rev. 2018 Oct;46(4):205-214. (PMID: 30001274)
Cell. 2014 Dec 18;159(7):1698-710. (PMID: 25497548)
Am J Med Genet A. 2008 Feb 15;146A(4):529-31. (PMID: 18203166)
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10876-10887. (PMID: 32354994)
Circulation. 2020 Aug 4;142(5):466-482. (PMID: 32403949)
Nature. 2020 Dec;588(7838):466-472. (PMID: 32971526)
Development. 1998 Sep;125(18):3615-23. (PMID: 9716527)
Cardiovasc Diabetol. 2018 Jun 8;17(1):83. (PMID: 29884191)
Nat Med. 2015 Jul;21(7):786-94. (PMID: 26053624)
Muscle Nerve. 2008 Nov;38(5):1405-1411. (PMID: 18816606)
Nat Methods. 2020 Jun;17(6):615-620. (PMID: 32366989)
Nat Methods. 2017 Sep 29;14(10):935-936. (PMID: 28960196)
Elife. 2020 Mar 09;9:. (PMID: 32149610)
Cold Spring Harb Perspect Biol. 2015 Feb 02;7(2):a006023. (PMID: 25646377)
Hum Mol Genet. 2017 Aug 1;26(15):2923-2932. (PMID: 28472301)
BMC Genomics. 2012 Oct 30;13:574. (PMID: 23110385)
Science. 2014 Sep 12;345(6202):1254665. (PMID: 25214635)
Immunity. 2021 Feb 9;54(2):259-275.e7. (PMID: 33382972)
Science. 2019 Sep 27;365(6460):1401-1405. (PMID: 31604266)
Sci Rep. 2021 Aug 19;11(1):16801. (PMID: 34413352)
Nat Biotechnol. 2018 Jan;36(1):89-94. (PMID: 29227470)
Commun Biol. 2019 Jan 7;2:9. (PMID: 30623105)
Cell. 2019 Jul 25;178(3):714-730.e22. (PMID: 31348891)
Nat Commun. 2018 Oct 22;9(1):4383. (PMID: 30348985)
Nat Rev Cardiol. 2019 Jan;16(1):56-68. (PMID: 30333526)
Nature. 2021 May;593(7860):575-579. (PMID: 33981032)
Nature. 1992 Feb 20;355(6362):696-702. (PMID: 1741056)
Cell Rep. 2018 Dec 18;25(12):3530-3542.e5. (PMID: 30566875)
Physiol Rev. 2018 Jul 1;98(3):1627-1738. (PMID: 29873596)
J Exp Med. 2017 Jul 3;214(7):1913-1923. (PMID: 28606987)
Dev Biol. 2009 Nov 15;335(2):407-17. (PMID: 19769957)
J Am Soc Nephrol. 2019 Jan;30(1):23-32. (PMID: 30510133)
J Immunol. 2005 Sep 1;175(5):2974-81. (PMID: 16116184)
Mol Cell. 2019 Aug 8;75(3):644-660.e5. (PMID: 31398325)
Mediators Inflamm. 2014;2014:136329. (PMID: 25214710)
Nat Genet. 2003 Jun;34(2):209-14. (PMID: 12766770)
Cell. 2020 Oct 29;183(3):666-683.e17. (PMID: 32991841)
Biochem Biophys Res Commun. 2004 Sep 24;322(3):887-92. (PMID: 15336546)
Eur Heart J. 2013 Aug;34(31):2436-43. (PMID: 23641007)
Genome Biol. 2019 Dec 19;20(1):290. (PMID: 31856883)
Circ Res. 2014 Apr 25;114(9):1422-34. (PMID: 24650916)
Science. 2019 Mar 15;363(6432):. (PMID: 30872492)
Sci Rep. 2021 Feb 18;11(1):4076. (PMID: 33603054)
Cell. 2019 Jul 25;178(3):686-698.e14. (PMID: 31257031)
Neurology. 2003 Jun 10;60(11):1854-7. (PMID: 12796551)
Science. 2020 Sep 11;369(6509):. (PMID: 32913075)
Nature. 2021 Jul;595(7865):107-113. (PMID: 33915569)
Nat Genet. 2003 Jun;34(2):203-8. (PMID: 12766769)
Science. 2019 Jun 28;364(6447):1287-1290. (PMID: 31249060)
Nat Genet. 2021 Nov;53(11):1527-1533. (PMID: 34711957)
Clin Immunol. 2009 Jun;131(3):501-9. (PMID: 19307157)
Nat Commun. 2020 Dec 11;11(1):6375. (PMID: 33311457)
Nucleic Acids Res. 2019 Jan 8;47(D1):D1038-D1043. (PMID: 30445645)
Skelet Muscle. 2021 May 17;11(1):13. (PMID: 34001262)
Mol Syst Biol. 2019 Jun 19;15(6):e8746. (PMID: 31217225)
Int J Biol Sci. 2014 Mar 27;10(4):438-47. (PMID: 24719561)
J Biol Chem. 2009 May 22;284(21):14524-36. (PMID: 19342381)
Nat Protoc. 2020 Apr;15(4):1484-1506. (PMID: 32103204)
J Pathol. 2020 Apr;250(5):705-714. (PMID: 32003464)
Sci Rep. 2020 Jan 14;10(1):229. (PMID: 31937892)
Cell Mol Life Sci. 2019 Apr;76(8):1507-1528. (PMID: 30770952)
Front Cell Neurosci. 2019 Feb 11;13:33. (PMID: 30804758)
J Cell Biol. 2012 May 28;197(5):677-89. (PMID: 22613833)
Nat Rev Mol Cell Biol. 2019 Aug;20(8):457-473. (PMID: 31182865)
Genome Biol. 2021 Jan 26;22(1):49. (PMID: 33499903)
Nat Rev Nephrol. 2018 Aug;14(8):479-492. (PMID: 29789704)
Nat Rev Genet. 2019 Aug;20(8):467-484. (PMID: 31068683)
Nature. 2018 Aug;560(7718):319-324. (PMID: 30069044)
Nat Biotechnol. 2021 Oct;39(10):1246-1258. (PMID: 34083792)
Endocr Regul. 2016 Apr;50(2):55-61. (PMID: 27560637)
Am J Respir Crit Care Med. 2019 Jun 15;199(12):1517-1536. (PMID: 30554520)
Commun Biol. 2022 Oct 12;5(1):1084. (PMID: 36224302)
Cardiovasc Res. 2004 Aug 1;63(2):196-207. (PMID: 15249177)
Muscle Nerve. 2008 Dec;38(6):1572-84. (PMID: 19016545)
J Clin Med. 2020 Apr 09;9(4):. (PMID: 32283761)
Am J Hum Genet. 2009 Sep;85(3):414-8. (PMID: 19732862)
Grant Information:: R21 HL161760 United States HL NHLBI NIH HHS; R56 HL157632 United States HL NHLBI NIH HHS; R21 HL156124 United States HL NHLBI NIH HHS; R01 EY031424 United States EY NEI NIH HHS; U41 HG009494 United States HG NHGRI NIH HHS; HHSN268201000029C United States HL NHLBI NIH HHS
Substance Nomenclature:: 0 (Biomarkers)
Entry Date(s):: Date Created: 20220513 Date Completed: 20220517 Latest Revision: 20231106
Update Code:: 20240105
PubMed Central ID:: PMC9383269
DOI:: 10.1126/science.abl4290
PMID:: 35549429
: Czasopismo naukowe

Pełny tekst

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

Comment in: Science. 2022 May 13;376(6594):695-696. (PMID: 35549410)
Comment in: Am J Transplant. 2022 Sep;22(9):2127-2128. (PMID: 36039543)
Comment in: Signal Transduct Target Ther. 2022 Oct 5;7(1):352. (PMID: 36198687)

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