果冻影院

The research, published today in Nature, could help expand treatment options for blood cancers like leukaemia and inherited blood disorders such as sickle cell disease.

Blood stem cells, also called hematopoietic stem cells, have the ability to make unlimited copies of themselves and to differentiate into every type of blood cell in the human body. For decades, doctors have used blood stem cells from the bone marrow of donors and the umbilical cords of newborns in life-saving transplant treatments for blood and immune diseases. However, these treatments are limited by a shortage of matched donors and hampered by the low number of stem cells in cord blood.

Researchers have sought to overcome these limitations by attempting to create blood stem cells in the lab from human pluripotent stem cells, which can potentially give rise to any cell type in the body. But success has been elusive, in part because scientists have lacked the instructions to make lab-grown cells differentiate into self-renewing blood stem cells rather than short-lived blood progenitor cells, which can only produce limited blood cell types.

Co-corresponding author of the research, Dr Vincenzo Calvanese (果冻影院 Laboratory for Molecular Cell Biology), who began the research at 果冻影院A before moving to 果冻影院 and completing the analysis, said: 鈥淧revious efforts to make functional blood stem cells in the lab have not been successful as we did not know enough about how these cells develop. Our new roadmap will help other scientists to understand fundamental differences between blood stem cells and short-lived progenitor cells.

鈥淲e now have a manual of how hematopoietic stem cells are made in the embryo and how they acquire the unique properties that make them useful for patients.鈥�

The research team, which also included scientists from Germany鈥檚 University of T眉bingen and Australia鈥檚 Murdoch Children鈥檚 Research Institute, created the resource using single-cell RNA sequencing and spatial transcriptomics, new technologies that enable scientists to identify the unique genetic networks and functions of thousands of individual cells and to reveal the location of these cells in the embryo.

The de-identified data are available to the public on the website听The Atlas of Human Hematopoietic Stem Cell Development.

The data make it possible to follow blood stem cells as they emerge from the hemogenic endothelium and migrate through various locations during their development, starting from the aorta and ultimately arriving in the bone marrow. Importantly, the map unveils specific milestones in their maturation process, including their arrival in the liver, where they acquire the special abilities of blood stem cells. The researchers explain that immature blood stem cells must move through different locations to learn how to do their job as blood stem cells.

The research group also pinpointed the exact precursor in the blood vessel wall that gives rise to blood stem cells. This discovery clarifies a longstanding controversy about the stem cells鈥� cellular origin and the environment that is needed to make a blood stem cell rather than a blood progenitor cell.

Now that the researchers have identified specific molecular signatures associated听with the different phases of human blood stem cell development, scientists can use this resource to see how close they are to making a transplantable blood stem cell in the lab.

Lead author Professor Hanna Mikkola (Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at 果冻影院A) said: 鈥淧reviously, if we tried to create a blood stem cell from a pluripotent cell and it didn鈥檛 transplant, we wouldn鈥檛 know where in the process we failed.

鈥淣ow, we can place the cells in our roadmap to see where we鈥檙e succeeding, where we鈥檙e falling short and fine-tune the differentiation process according to the instructions from the embryo.鈥�

In addition, the map can help scientists understand how blood-forming cells that develop in the embryo contribute to human disease. For example, it provides the foundation for studying why some blood cancers that begin in utero are more aggressive than those that occur after birth.

Professor Mikkola added: 鈥淣ow that we鈥檝e created an online resource that scientists around the world can use to guide their research, the real work is starting. It鈥檚 a really exciting time to be in the field because we鈥檙e finally going to be seeing the fruits of our labour.鈥�

The research was supported by the National Institutes of Health, the 果冻影院A Jonsson Cancer Center Foundation, the David Geffen School of Medicine at 果冻影院A, the Swedish Research Council, the European Molecular Biology Organization, the Swiss National Science Foundation and the 果冻影院A Broad Stem Cell Research Center (including support from the Rose Hills Foundation and the centre鈥檚 training program).

Links

• 果冻影院 Laboratory for Molecular Cell Biology

Source

• 果冻影院A

Image

• Human blood stem cells emerging from specialised endothelial cells in the wall of an embryonic aorta. 果冻影院A scientists鈥� confirmation of this process clarifies a longstanding controversy about the stem cells鈥� cellular origin. Credit: Hanna Mikkola Lab/果冻影院A, Katja Schenke-Layland Lab/University of T眉bingen, Nature

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