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

Autor: Segal JM; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. joe.segal@kcl.ac.uk., Kent D; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Wesche DJ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94304, USA., Ng SS; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Serra M; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Oulès B; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Kar G; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Emerton G; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Blackford SJI; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Darmanis S; School of Engineering, Stanford University, Stanford, 94350, CA, USA., Miquel R; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Luong TV; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Yamamoto R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA., Bonham A; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA., Jassem W; Institute of Liver Studies, Kings College Hospital, London, SE4 9RS, UK., Heaton N; Institute of Liver Studies, Kings College Hospital, London, SE4 9RS, UK., Vigilante A; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., King A; Department of Diabetes, King's College London, London, SE1 1UL, UK., Sancho R; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK., Teichmann S; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Quake SR; School of Engineering, Stanford University, Stanford, 94350, CA, USA., Nakauchi H; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA., Rashid ST; Centre for Stem Cells and Regenerative Medicine & Institute for Liver Studies, King's College London, London, WC2R 2LS, UK. tamir.rashid@kcl.ac.uk.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA. tamir.rashid@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Jul 26; Vol. 10 (1), pp. 3350. Date of Electronic Publication: 2019 Jul 26.
DOI: 10.1038/s41467-019-11266-x
Abstrakt: 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.
Databáze: MEDLINE