Precursor to blood-forming stem cells determined in human embryo
Catherine Turnbull, Progress Educational Trust
23 May 2022

[BioNews, London]

Precursors to the stem cells that make blood have been derived in vitro from human pluripotent stem cells for the first time.

Human pluripotent stem cells (hPSCs) can become most other types of human cells, depending on the chemical signals they are exposed to. Researchers from the USA and Italy have determined the necessary factors for developing the precursors to haematopoietic stem cells: the cells found in bone marrow which make every type of human blood cell. 

'Here, we identified for the first time, a progenitor population that positively responds to retinoic acid to give rise to blood progenitors,' senior author Dr Christopher Sturgeon from Mount Sinai School of Medicine, New York, told Genetic Engineering and Biotechnology News.

The study, published in Nature Cell Biology, also noted that the cells created were similar to those which occur during human embryonic development. 

'Remarkably, these responsive cells are at a developmental stage equivalent to the very early human embryo – around 19 days of gestation – which is much earlier than previously assumed based on mouse developmental studies. Now we can focus on how to properly guide, with additional signals, the maturation of these cells into a blood-forming stem cell,' said Dr Sturgeon.

Within a developing embryo, a layer of cells known as the haemogenic endothelium requires retinoic acid – the active form of vitamin A – to produce haematopoietic stem cells. This study used single-cell RNA sequencing on the hPSCs, to show that two distinct cell populations are formed: either through a retinoic-dependent or independent manner. Whole-transcriptome analysis highlighted that these distinct cell types are like those found within the human embryo, with the retinoic acid-dependent population deriving precursors to blood-forming stem cells.

'Now we can focus our efforts at understanding how to capture embryonic blood-forming stem cells, with the goal of using them as a substitute for bone marrow,' said Dr Sturgeon.

The researchers hope that their findings could eventually save lives. Transplants of hematopoetic stem cells can be a lifesaving form of treatment for people with some cancers and other conditions such as sickle cell. These stem cells are currently obtained from donors but producing them from hPSCs in vitro could reduce waiting times, or difficulties finding a donor who is a good match.

SOURCES & REFERENCES

Blood precursor cell requiring retinoic acid identified
Genetic Engineering and Biotechnology News |  29 April 2022
Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells
Nature Cell Biology |  28 April 2022
Researchers share insights about mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture
Mount Sinai Health System |  27 April 2022





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