Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-Parenchymal Cell Lineages
This week we profile a recent publication in Cell from the laboratory of Dr. Pamela Hoodless (pictured, right) at BC Cancer.
Can you provide a brief overview of your lab’s current research focus?
The Hoodless laboratory explores regulatory mechanisms in organ development, in particular the liver and heart valves. Using state of the art genomic technologies, the team endeavours to shed new light on developmental gene networks by using whole tissue and single cell analyses of gene expression, transcription factor function and epigenetic mechanisms.
What is the significance of the findings in this publication?
Our paper uses single-cell transcriptomics to assess the developmental origins of the three main cell types within the embryonic liver. Specifically, we characterize the emergence of previously uncharacterized mesenchymal populations, the development of liver sinusoidal endothelial cells, the specification of hepatoblasts from the endoderm, and the signaling microenvironment during liver formation. Of interest, we capture a novel cell type within the liver, which we have termed the hepatomesenchyme. This cell type expresses a hybrid gene profile reminiscent of both hepatic and mesenchymal cell identities, and emerges just as hepatoblasts migrate out of the endoderm, suggesting involvement in the formation of the liver bud. In sum, our publication provides a comprehensive atlas of liver formation at single-cell resolution, serving as a resource for the investigation of early liver development that may help inform future regenerative medicine approaches to liver disease. Our data is available to explore at the Broad Single-Cell Portal.
What are the next steps for this research?
We plan on using in vivo and in vitro techniques to add to our findings. Specifically, we’re interested in validating the candidate cell-cell interactions in the normal development of hepatic sinusoidal endothelial cells, which are a clinically relevant cell type whose dysfunction and dedifferentiation often drive liver disease. We further plan to characterize the role of the hepatomesenchyme in liver development and use lineage tracing to determine contribution of its descendents to the mature liver.
This work was funded by:
- Natural Sciences and Research Council of Canada (NSERC)
- the Canadian Institutes of Health Research (CIHR)
- Genome BC
- the Canadian Foundation for Innovation
- the British Columbia Knowledge Development Fund
- 10X Genomics