Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity
Background & Aims: The multiple vital functions of the human liver are performed by highly specialised parenchymal and non-parenchymal cells organised in complex collaborative sinusoidal units. Although crucial for homeostasis, the cellular make-up of the human liver remains to be fully eluc...
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Format: | Article |
Language: | English |
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Elsevier
2021-06-01
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Series: | JHEP Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555921000549 |
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doaj-dba9693007174f0d8a6f05b5c1adca53 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valéry L. Payen Arnaud Lavergne Niki Alevra Sarika Megan Colonval Latifa Karim Manon Deckers Mustapha Najimi Wouter Coppieters Benoît Charloteaux Etienne M. Sokal Adil El Taghdouini |
spellingShingle |
Valéry L. Payen Arnaud Lavergne Niki Alevra Sarika Megan Colonval Latifa Karim Manon Deckers Mustapha Najimi Wouter Coppieters Benoît Charloteaux Etienne M. Sokal Adil El Taghdouini Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity JHEP Reports Liver cell atlas Hepatocyte Zonation Extracellular matrix |
author_facet |
Valéry L. Payen Arnaud Lavergne Niki Alevra Sarika Megan Colonval Latifa Karim Manon Deckers Mustapha Najimi Wouter Coppieters Benoît Charloteaux Etienne M. Sokal Adil El Taghdouini |
author_sort |
Valéry L. Payen |
title |
Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity |
title_short |
Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity |
title_full |
Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity |
title_fullStr |
Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity |
title_full_unstemmed |
Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity |
title_sort |
single-cell rna sequencing of human liver reveals hepatic stellate cell heterogeneity |
publisher |
Elsevier |
series |
JHEP Reports |
issn |
2589-5559 |
publishDate |
2021-06-01 |
description |
Background & Aims: The multiple vital functions of the human liver are performed by highly specialised parenchymal and non-parenchymal cells organised in complex collaborative sinusoidal units. Although crucial for homeostasis, the cellular make-up of the human liver remains to be fully elucidated. Here, single-cell RNA-sequencing was used to unravel the heterogeneity of human liver cells, in particular of hepatocytes (HEPs) and hepatic stellate cells (HSCs). Method: The transcriptome of ~25,000 freshly isolated human liver cells was profiled using droplet-based RNA-sequencing. Recently published data sets and RNA in situ hybridisation were integrated to validate and locate newly identified cell populations. Results: In total, 22 cell populations were annotated that reflected the heterogeneity of human parenchymal and non-parenchymal liver cells. More than 20,000 HEPs were ordered along the portocentral axis to confirm known, and reveal previously undescribed, zonated liver functions. The existence of 2 subpopulations of human HSCs with unique gene expression signatures and distinct intralobular localisation was revealed (i.e. portal and central vein-concentrated GPC3+ HSCs and perisinusoidally located DBH+ HSCs). In particular, these data suggest that, although both subpopulations collaborate in the production and organisation of extracellular matrix, GPC3+ HSCs specifically express genes involved in the metabolism of glycosaminoglycans, whereas DBH+ HSCs display a gene signature that is reminiscent of antigen-presenting cells. Conclusions: This study highlights metabolic zonation as a key determinant of HEP transcriptomic heterogeneity and, for the first time, outlines the existence of heterogeneous HSC subpopulations in the human liver. These findings call for further research on the functional implications of liver cell heterogeneity in health and disease. Lay summary: This study resolves the cellular landscape of the human liver in an unbiased manner and at high resolution to provide new insights into human liver cell biology. The results highlight the physiological heterogeneity of human hepatic stellate cells. |
topic |
Liver cell atlas Hepatocyte Zonation Extracellular matrix |
url |
http://www.sciencedirect.com/science/article/pii/S2589555921000549 |
work_keys_str_mv |
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doaj-dba9693007174f0d8a6f05b5c1adca532021-06-05T06:10:30ZengElsevierJHEP Reports2589-55592021-06-0133100278Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneityValéry L. Payen0Arnaud Lavergne1Niki Alevra Sarika2Megan Colonval3Latifa Karim4Manon Deckers5Mustapha Najimi6Wouter Coppieters7Benoît Charloteaux8Etienne M. Sokal9Adil El Taghdouini10Laboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium; Laboratory of Advanced Drug Delivery and Biomaterials (ADDB), LDRI Institute, Université catholique de Louvain, Brussels, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium; Laboratory of Advanced Drug Delivery and Biomaterials (ADDB), LDRI Institute, Université catholique de Louvain, Brussels, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumGenomics Platform, GIGA Institute, Université de Liège, Liège, BelgiumLaboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium; Corresponding authors. Address: Laboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Avenue Mounier 52 Box B1.52.03, 1200 Brussels, Belgium.Laboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Brussels, Belgium; Corresponding authors. Address: Laboratory of Pediatric Hepatology and Cell Therapy (PEDI), IREC Institute, Université catholique de Louvain, Avenue Mounier 52 Box B1.52.03, 1200 Brussels, Belgium.Background & Aims: The multiple vital functions of the human liver are performed by highly specialised parenchymal and non-parenchymal cells organised in complex collaborative sinusoidal units. Although crucial for homeostasis, the cellular make-up of the human liver remains to be fully elucidated. Here, single-cell RNA-sequencing was used to unravel the heterogeneity of human liver cells, in particular of hepatocytes (HEPs) and hepatic stellate cells (HSCs). Method: The transcriptome of ~25,000 freshly isolated human liver cells was profiled using droplet-based RNA-sequencing. Recently published data sets and RNA in situ hybridisation were integrated to validate and locate newly identified cell populations. Results: In total, 22 cell populations were annotated that reflected the heterogeneity of human parenchymal and non-parenchymal liver cells. More than 20,000 HEPs were ordered along the portocentral axis to confirm known, and reveal previously undescribed, zonated liver functions. The existence of 2 subpopulations of human HSCs with unique gene expression signatures and distinct intralobular localisation was revealed (i.e. portal and central vein-concentrated GPC3+ HSCs and perisinusoidally located DBH+ HSCs). In particular, these data suggest that, although both subpopulations collaborate in the production and organisation of extracellular matrix, GPC3+ HSCs specifically express genes involved in the metabolism of glycosaminoglycans, whereas DBH+ HSCs display a gene signature that is reminiscent of antigen-presenting cells. Conclusions: This study highlights metabolic zonation as a key determinant of HEP transcriptomic heterogeneity and, for the first time, outlines the existence of heterogeneous HSC subpopulations in the human liver. These findings call for further research on the functional implications of liver cell heterogeneity in health and disease. Lay summary: This study resolves the cellular landscape of the human liver in an unbiased manner and at high resolution to provide new insights into human liver cell biology. The results highlight the physiological heterogeneity of human hepatic stellate cells.http://www.sciencedirect.com/science/article/pii/S2589555921000549Liver cell atlasHepatocyteZonationExtracellular matrix |