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Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.
Συγγραφείς: Andrews TS; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Atif J; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.; Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada., Liu JC; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; The Donnelly Centre, Toronto, ON, Canada., Perciani CT; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.; Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Ma XZ; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Thoeni C; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Slyper M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Eraslan G; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Segerstolpe A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Manuel J; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Chung S; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Winter E; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Cirlan I; Princess Margaret Genome Centre, University Health Network, Toronto, ON, Canada., Khuu N; Princess Margaret Genome Centre, University Health Network, Toronto, ON, Canada., Fischer S; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA.; Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., McGilvray ID; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada., Bader GD; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; The Donnelly Centre, Toronto, ON, Canada., MacParland SA; Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.; Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Πηγή: Hepatology communications [Hepatol Commun] 2022 Apr; Vol. 6 (4), pp. 821-840. Date of Electronic Publication: 2021 Nov 18.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 101695860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2471-254X (Electronic) Linking ISSN: 2471254X NLM ISO Abbreviation: Hepatol Commun Subsets: MEDLINE
Imprint Name(s): Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc. on behalf of the American Association for the Study of Liver Diseases, [2017]-
Ιατρικοί όροι (MeSH): Liver* , Single-Cell Analysis*, Cell Nucleus/genetics ; Transcriptome/genetics ; Humans ; Sequence Analysis, RNA
Περίληψη: The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation-related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at a single-cell resolution, revealed the presence of rare subtypes of liver mesenchymal cells, and facilitated the detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and natural killer cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte, and mesenchymal cell populations by an independent spatial transcriptomics data set and immunohistochemistry. Conclusion: Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.
(© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
References: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D168-70. (PMID: 14681386)
World J Gastroenterol. 2006 Jun 14;12(22):3496-511. (PMID: 16773707)
Nat Med. 2020 May;26(5):792-802. (PMID: 32405060)
Mol Syst Biol. 2020 Dec;16(12):e9682. (PMID: 33332768)
Clin Gastroenterol Hepatol. 2005 Apr;3(4):384-9. (PMID: 15822044)
Nature. 2019 Aug;572(7768):199-204. (PMID: 31292543)
PLoS One. 2011;6(9):e24568. (PMID: 21931759)
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BMC Genomics. 2018 Jun 19;19(1):477. (PMID: 29914354)
Bioinformatics. 2016 Apr 15;32(8):1241-3. (PMID: 26668002)
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Nat Commun. 2013;4:2823. (PMID: 24264436)
Science. 2015 Jan 23;347(6220):1260419. (PMID: 25613900)
Cell. 2020 Oct 15;183(2):377-394.e21. (PMID: 32976798)
Science. 2007 Feb 16;315(5814):972-6. (PMID: 17218491)
Nat Med. 2020 Dec;26(12):1899-1911. (PMID: 33106666)
Compr Physiol. 2013 Jan;3(1):541-65. (PMID: 23720296)
Nucleic Acids Res. 2021 Jan 8;49(D1):D1541-D1547. (PMID: 33174596)
Sci Rep. 2020 Jan 30;10(1):1535. (PMID: 32001747)
Nat Methods. 2019 Dec;16(12):1289-1296. (PMID: 31740819)
Nature. 2019 Nov;575(7783):512-518. (PMID: 31597160)
Cell Rep. 2019 Nov 12;29(7):1832-1847.e8. (PMID: 31722201)
Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):397-411. (PMID: 28487545)
Nat Methods. 2018 May;15(5):359-362. (PMID: 29608555)
Trends Genet. 2013 Oct;29(10):569-74. (PMID: 23810203)
Exp Hematol. 2004 Jul;32(7):585-98. (PMID: 15246154)
Nature. 2017 Feb 16;542(7641):352-356. (PMID: 28166538)
Nat Rev Gastroenterol Hepatol. 2019 May;16(5):269-281. (PMID: 30850822)
J Biol Chem. 2000 Jan 28;275(4):2247-50. (PMID: 10644669)
Nat Methods. 2017 Sep 29;14(10):935-936. (PMID: 28960196)
Hepatobiliary Surg Nutr. 2014 Dec;3(6):344-63. (PMID: 25568859)
Nat Commun. 2018 Oct 22;9(1):4383. (PMID: 30348985)
Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):E3297-305. (PMID: 25074909)
J Am Soc Nephrol. 2019 Jan;30(1):23-32. (PMID: 30510133)
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N Engl J Med. 2016 Sep 22;375(12):1161-70. (PMID: 27653566)
Nat Commun. 2019 Jul 26;10(1):3350. (PMID: 31350390)
Grant Information: P41 GM103504 United States GM NIGMS NIH HHS; R01 HG009979 United States HG NHGRI NIH HHS
Entry Date(s): Date Created: 20211118 Date Completed: 20220405 Latest Revision: 20230113
Update Code: 20260130
PubMed Central ID: PMC8948611
DOI: 10.1002/hep4.1854
PMID: 34792289
Βάση Δεδομένων: MEDLINE
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  Data: Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.
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  Data: The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation-related cell perturbation can limit the ability to fully capture the human liver's parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq). The addition of snRNA-seq enabled the characterization of interzonal hepatocytes at a single-cell resolution, revealed the presence of rare subtypes of liver mesenchymal cells, and facilitated the detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and natural killer cells were only distinguishable using scRNA-seq, highlighting the importance of applying both technologies to obtain a complete map of tissue-resident cell types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte, and mesenchymal cell populations by an independent spatial transcriptomics data set and immunohistochemistry. Conclusion: Our study provides a systematic comparison of the transcriptomes captured by scRNA-seq and snRNA-seq and delivers a high-resolution map of the parenchymal cell populations in the healthy human liver.<br /> (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
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            NameFull: Khuu N
      – PersonEntity:
          Name:
            NameFull: Fischer S
      – PersonEntity:
          Name:
            NameFull: Rozenblatt-Rosen O
      – PersonEntity:
          Name:
            NameFull: Regev A
      – PersonEntity:
          Name:
            NameFull: McGilvray ID
      – PersonEntity:
          Name:
            NameFull: Bader GD
      – PersonEntity:
          Name:
            NameFull: MacParland SA
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 04
              Text: 2022 Apr
              Type: published
              Y: 2022
          Identifiers:
            – Type: issn-electronic
              Value: 2471-254X
          Numbering:
            – Type: volume
              Value: 6
            – Type: issue
              Value: 4
          Titles:
            – TitleFull: Hepatology communications
              Type: main
ResultId 1