Blood stem cell analysis may hold key to laboratory blood production

17 December 2020

CRM scientists have used machine learning to compare blood stem cells grown in the lab with those generated in the body, identifying differences that may help improve the production of blood stem cells in the laboratory.

Blood stem cells are used to treat blood and bone marrow disorders and patients recovering from cancer treatment. However, these procedures are reliant on a limited blood donor supply and donor matches.

Production of blood cells in the laboratory from pluripotent stem cells (cells with the ability to generate all specialised cell types in an organism) could provide an alternative source for the treatment of disease. 

Blood progenitors (cells that are capable of differentiating into all the mature blood cell types) can be produced from pluripotent stem cells but it has not been possible to generate the most potent blood stem cells that are able to reconstitute the entire blood system.

This new research, led by Professor Lesley Forrester and Dr Antonella Fidanza, is the first to use machine learning to compare cells that are generated from pluripotent stem cells in the lab with the cells that are generated in the body.

The team used single cell RNA sequencing of blood cell progenitors derived from human pluripotent stem cells to define their transcriptome (a snapshot of the genes that are switched on or off in the cell). This was then compared to the transcriptome of blood stem and progenitor cells generated in the foetal liver of human embryos.

Fidanza and colleagues have identified a very small population of cells generated in the lab that are very similar to the haematopoietic (blood) stem cells that would be capable of reconstituting the entire blood system. They also identified transcriptional differences that might explain why past attempts to generate functional blood stem cells from pluripotent stem cells have failed.

Professor Forrester said,

These findings could ultimately be exploited to improve the production of blood stem cells in the laboratory, providing an alternative supply of blood for treating diseases such as leukaemia.

Blood cell progenitors grown in the lab from pluripotent stem cells.
Left: Blood cell progenitors grown in the lab from pluripotent stem cells. Right: Here the authors show expression of SPINK2, a known marker of haematopoietic stem cells by browsing their data in a new interactive website

The research is published, together with an expert commentary, in Blood and was funded by the Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council and Carnegie Trust.

The paper in Blood

Interactive website for visualising data from the paper

Lesley Forrester research group page