• Comprehensive map of human blood stem ce

    From ScienceDaily@1:317/3 to All on Wed Apr 13 22:30:44 2022
    Comprehensive map of human blood stem cell development

    Date:
    April 13, 2022
    Source:
    University of California - Los Angeles
    Summary:
    Scientists have created a new roadmap that traces each step in
    the development of blood stem cells in the human embryo, providing
    scientists with a blueprint for producing fully functional blood
    stem cells in the lab. The research could help expand treatment
    options for blood cancers like leukemia and inherited blood
    disorders such as sickle cell disease.



    FULL STORY ==========================================================================
    UCLA scientists and colleagues have created a first-of-its-kind roadmap
    that traces each step in the development of blood stem cells in the
    human embryo, providing scientists with a blueprint for producing fully functional blood stem cells in the lab.


    ==========================================================================
    The research, published today in the journal Nature, could help expand treatment options for blood cancers like leukemia and inherited blood
    disorders such as sickle cell disease, said Dr. Hanna Mikkola of the Eli
    and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
    at UCLA, who led the study.

    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.

    "Nobody has succeeded in making functional blood stem cells from human pluripotent stem cells because we didn't know enough about the cell we
    were trying to generate," said Mikkola, who is a professor of molecular,
    cell and developmental biology in the UCLA College and a member of the
    UCLA Jonsson Comprehensive Cancer Center.

    The new roadmap will help researchers understand the fundamental
    differences between the two cell types, which is critical for creating
    cells that are suitable for use in transplantation therapies, said UCLA scientist Vincenzo Calvanese, a co-first author of the research, along
    with UCLA's Sandra Capellera-Garcia and Feiyang Ma.



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    "We 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," said Calvanese, who is also a group leader at University
    College London. The de-identified data are available to the public on
    the website The Atlas of Human Hematopoietic Stem Cell Development.

    The research team, which included scientists from Germany's University of Tu"bingen and Australia's Murdoch Children's 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 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.

    To explain the maturation process, Mikkola compares immature blood
    stem cells to aspiring surgeons. Just as surgeons need to go through
    different stages of training to learn how to perform surgeries, 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' 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 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.

    "Previously, if we tried to create a blood stem cell from a pluripotent
    cell and it didn't transplant, we wouldn't know where in the process we failed," Mikkola said. "Now, we can place the cells in our roadmap to
    see where we're succeeding, where we're falling short and fine-tune the differentiation process according to the instructions from the embryo."
    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.

    "Now that we've created an online resource that scientists around the
    world can use to guide their research, the real work is starting,"
    Mikkola said. "It's a really exciting time to be in the field because
    we're finally going to be seeing the fruits of our labor." The research
    was supported by the National Institutes of Health, the UCLA Jonsson
    Cancer Center Foundation, the David Geffen School of Medicine at UCLA, the Swedish Research Council, the European Molecular Biology Organization,
    the Swiss National Science Foundation and the UCLA Broad Stem Cell
    Research Center (including support from the Rose Hills Foundation and
    the center's training program).


    ========================================================================== Story Source: Materials provided by
    University_of_California_-_Los_Angeles. Original written by Linda
    Wang. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Vincenzo Calvanese, Sandra Capellera-Garcia, Feiyang Ma, Iman Fares,
    Simone Liebscher, Elizabeth S. Ng, Sophia Ekstrand, Ju'lia
    Aguade'- Gorgorio', Anastasia Vavilina, Diane Lefaudeux, Brian
    Nadel, Jacky Y. Li, Yanling Wang, Lydia K. Lee, Reza Ardehali,
    M. Luisa Iruela-Arispe, Matteo Pellegrini, Ed G. Stanley, Andrew
    G. Elefanty, Katja Schenke-Layland, Hanna K. A. Mikkola. Mapping
    human haematopoietic stem cells from haemogenic endothelium to
    birth. Nature, 2022; DOI: 10.1038/s41586-022- 04571-x ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220413131150.htm

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