Novel research, employing single-cell RNA sequencing, has characterized a new liver cell population that may be capable of liver tissue regeneration. This has potential for treating liver diseases without the need for whole organ transplants.
Liver disease is the third most common cause of mortality in the UK. Currently, the only treatment for severe liver disease comprises whole liver transplantation. New research, conducted at King’s College London (UK), has utilized single-cell RNA sequencing to characterize the transcriptional profile of a unique population of cells and demonstrate that these hepatobiliary hybrid progenitor cells (HHyPs), found in the human fetal liver, strongly resemble mouse stem cells. These have the potential to rapidly regenerate and repair liver tissue following injury.
The regenerative capacity of the rodent liver is well characterized. It is proposed that similar regeneration may be feasible in the human adult liver. This would involve a population of ‘progenitor-like’ liver cells being re-activated following injury, such that they may develop into required liver cells. However, the large, obscuring overlap in transcriptional markers expressed in progenitor cell candidates and other mature liver cell populations has made evidencing this process difficult.
Single cell RNA sequencing has previously been utilized to discover unidentified cell types in cell populations formerly viewed as homogenous.
HHyPs form during early development and HHyP-like cells have been detected in small numbers in the human adult liver. Employing single-cell RNA sequencing, researchers characterized the transcriptional profile of fetal HHyPs and distinguished these from fetal hepatocytes and mature biliary epithelial cells.
Researchers subsequently isolated HHyPs from human fetal liver samples using fluorescence-activated cell sorting (FACS). The HHyP cells were found capable of developing into adult liver cell types.
Tamir Rashid, lead study author from the Centre for Stem Cells & Regenerative Medicine at King’s College, commented that the team’s findings “…could provide a wide range of regenerative medicine applications for treating liver disease, including the possibility of bypassing the need for liver transplants.”
Rashid continued: “We now need to work quickly to unlock the recipe for converting pluripotent stem cells into HHyPs so that we could transplant those cells into patients at will. In the longer term, we will also be working to see if we can reprogram HHyPs within the body using traditional pharmacological drugs to repair diseased livers without either cell or organ transplantation.”
Segal JM, Kent D, Wesche DJ et al. Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors. Nat. Commun; 10(1); (2019);