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Nature communications
07 26, 2019;10 (1): 3350.

Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors.

Joe M Segal, Deniz Kent, Daniel J Wesche, Soon Seng Ng, Maria Serra, Bénédicte Oulès, Gozde Kar, Guy Emerton, Samuel J I Blackford, Spyros Darmanis, Rosa Miquel, Tu Vinh Luong, Ryo Yamamoto, Andrew Bonham, Wayel Jassem, Nigel Heaton, Alessandra Vigilante, Aileen King, Rocio Sancho, Sarah Teichmann, Stephen R Quake, Hiromitsu Nakauchi, S Tamir Rashid
Author Information
  1. Joe M Segal: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. joe.segal@kcl.ac.uk. ORCID
  2. Deniz Kent: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK.
  3. Daniel J Wesche: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  4. Soon Seng Ng: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. ORCID
  5. Maria Serra: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK.
  6. Bénédicte Oulès: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. ORCID
  7. Gozde Kar: Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
  8. Guy Emerton: Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
  9. Samuel J I Blackford: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. ORCID
  10. Spyros Darmanis: School of Engineering, Stanford University, Stanford, 94350, CA, USA.
  11. Rosa Miquel: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK.
  12. Tu Vinh Luong: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK.
  13. Ryo Yamamoto: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  14. Andrew Bonham: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  15. Wayel Jassem: Institute of Liver Studies, Kings College Hospital, London, SE4 9RS, UK.
  16. Nigel Heaton: Institute of Liver Studies, Kings College Hospital, London, SE4 9RS, UK.
  17. Alessandra Vigilante: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK.
  18. Aileen King: Department of Diabetes, King's College London, London, SE1 1UL, UK.
  19. Rocio Sancho: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. ORCID
  20. Sarah Teichmann: Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK. ORCID
  21. Stephen R Quake: School of Engineering, Stanford University, Stanford, 94350, CA, USA.
  22. Hiromitsu Nakauchi: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  23. S Tamir Rashid: Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. tamir.rashid@kcl.ac.uk.
PMID: 31350390 DOI: 10.1038/s41467-019-11266-x

Abstract

The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.

References

  1. Nat Protoc. 2014 Jan;9(1):171-81 [PMID: 24385147]
  2. Cell. 2018 Sep 20;175(1):43-56.e21 [PMID: 30241615]
  3. Nat Genet. 2011 Jan;43(1):34-41 [PMID: 21113154]
  4. Nature. 2017 Jul 20;547(7663):350-354 [PMID: 28700576]
  5. Stem Cell Reports. 2013 Oct 10;1(4):293-306 [PMID: 24319665]
  6. Nat Commun. 2018 Oct 22;9(1):4383 [PMID: 30348985]
  7. Nat Cell Biol. 2015 Aug;17(8):971-983 [PMID: 26192438]
  8. Bioinformatics. 2015 Jan 15;31(2):166-9 [PMID: 25260700]
  9. Nature. 2013 Feb 14;494(7436):247-50 [PMID: 23354049]
  10. PLoS One. 2010 Jun 04;5(6):e10965 [PMID: 20532031]
  11. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9912-7 [PMID: 16782807]
  12. Cell Stem Cell. 2018 Jul 05;23(1):114-122.e3 [PMID: 29937200]
  13. Cell. 2015 Jan 15;160(1-2):299-312 [PMID: 25533785]
  14. Cell Stem Cell. 2017 Jan 5;20(1):41-55 [PMID: 27840021]
  15. Gut. 2005 Jul;54(7):972-9 [PMID: 15951545]
  16. Int J Clin Exp Pathol. 2013 Apr 15;6(5):889-96 [PMID: 23638220]
  17. Stem Cells Dev. 2014 Sep 1;23(17):2119-25 [PMID: 24800694]
  18. Int J Cancer. 2006 Oct 15;119(8):1920-6 [PMID: 16804906]
  19. Stem Cell Res. 2009 May;2(3):198-210 [PMID: 19393593]
  20. Nature. 2003 May 22;423(6938):448-52 [PMID: 12717451]
  21. Stem Cell Reports. 2018 Mar 13;10(3):751-765 [PMID: 29503086]
  22. Stem Cell Reports. 2017 Aug 8;9(2):478-489 [PMID: 28689996]
  23. J Hepatol. 2019 Jan;70(1):97-107 [PMID: 30240598]
  24. Development. 2009 Jun;136(11):1951-60 [PMID: 19429791]
  25. Liver Int. 2004 Feb;24(1):29-37 [PMID: 15101998]
  26. Genome Biol. 2016 May 12;17:103 [PMID: 27176874]
  27. Stem Cells. 2006 Aug;24(8):1852-8 [PMID: 16627685]
  28. Cell Rep. 2017 Oct 31;21(5):1399-1410 [PMID: 29091775]
  29. Cell Stem Cell. 2014 Sep 4;15(3):340-349 [PMID: 25130492]
  30. Cell. 2015 Aug 13;162(4):766-79 [PMID: 26276631]
  31. Biochim Biophys Acta. 2009 Dec;1796(2):309-14 [PMID: 19683559]
  32. Nat Biotechnol. 2015 Aug;33(8):845-852 [PMID: 26167629]
  33. J Invest Dermatol. 2018 Apr;138(4):811-825 [PMID: 29391249]
  34. Am J Pathol. 1999 Feb;154(2):537-41 [PMID: 10027411]
  35. Cell. 2015 Jan 15;160(1-2):285-98 [PMID: 25594184]
  36. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 [PMID: 16199517]
  37. Cell Res. 2019 Jan;29(1):8-22 [PMID: 30361550]
  38. J Cell Physiol. 2009 Jul;220(1):72-81 [PMID: 19229878]
  39. J Exp Med. 2007 Aug 6;204(8):1973-87 [PMID: 17664288]
  40. Cell Stem Cell. 2015 Sep 3;17(3):353-9 [PMID: 26299572]
  41. Bioinformatics. 2017 Apr 15;33(8):1179-1186 [PMID: 28088763]
  42. Hepatology. 2017 Nov;66(5):1387-1401 [PMID: 28681484]
  43. Hepatology. 2011 Mar;53(3):1035-45 [PMID: 21374667]
  44. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  45. Nature. 2014 May 15;509(7500):371-5 [PMID: 24739965]
  46. Peptides. 2004 May;25(5):763-70 [PMID: 15177870]
  47. Nat Biotechnol. 2014 Apr;32(4):381-386 [PMID: 24658644]
  48. Hepatology. 2007 Jan;45(1):139-49 [PMID: 17187413]
  49. Genes Dev. 2005 Aug 15;19(16):1849-54 [PMID: 16103213]
  50. Nat Med. 2017 Aug;23(8):954-963 [PMID: 28671689]
  51. Nature. 2015 Aug 13;524(7564):180-5 [PMID: 26245375]
  52. Nature. 2008 Dec 11;456(7223):804-8 [PMID: 18946470]
  53. Curr Opin Genet Dev. 2004 Oct;14(5):582-90 [PMID: 15380251]
  54. Sci Rep. 2017 Jan 04;7:39990 [PMID: 28051157]
  55. Cell Stem Cell. 2014 Nov 6;15(5):605-18 [PMID: 25312494]
  56. Nature. 2018 May;557(7704):247-251 [PMID: 29720662]
  57. Tumour Biol. 2012 Oct;33(5):1619-28 [PMID: 22610942]

Grants

  1. MR/L006537/1/Medical Research Council
  2. MR/S000011/1/Medical Research Council
  3. R01 AI099245/NIAID NIH HHS
  4. U19 AI109662/NIAID NIH HHS

MeSH Term

Antigens, Neoplasm
Cell Adhesion Molecules
Epithelial Cell Adhesion Molecule
Fetus
Hepatocytes
Humans
Liver
Single-Cell Analysis
Stem Cells
Transcription, Genetic

Chemicals

Antigens, Neoplasm
Cell Adhesion Molecules
EPCAM protein, human
Epithelial Cell Adhesion Molecule
TACSTD2 protein, human
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000029 (Single cell analysis of human fetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors)

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