PHILADELPHIA – A research team led by Nancy Speck, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, has discovered a molecular marker for the immediate precursors of hematopoietic (blood) stem cells (HSCs) in the developing embryo, which provides much-needed insights for making these cells from engineered precursors.
Because HSCs, found in the bone marrow of adult mammals, generate all of the blood cell types of the body, unlocking the secrets of their origin may help researchers to better manipulate embryonic stem cells to generate new blood cells for therapy. Speck is also an Investigator with the Abramson Family Cancer Research Institute at Penn. The work was published this week in Cell Stem Cell.
“The ultimate goal for stem-cell therapies is to take precursor stem cells and push them down a particular lineage to replace diseased or dead cells in human adults or children,” says Speck. First things first, she says: “You have to understand how this happens in the embryo.”
Previous studies indicated that HSCs originated from a small population of cells lining blood vessels, called endothelial cells. But, it was unclear precisely which endothelial cells transitioned to blood stem cells during early development.
In the embryo, there are multiple waves of blood-cell development. The first wave gives the embryo a quick oxygen source and the final wave sets up the development of HSCs that ultimately reside in adult bone marrow. The first wave of progenitors can be generated in the lab from embryonic or induced pluripotent stem cells, but efforts to produce hematopoietic stem cells have failed, says Speck.
“Understanding the developmental origins of hematopoietic stem cells is important for learning how to produce them in the lab from embryonic or induced pluripotent stem cells,” says Speck.
How much closer does this study take hematologists to be able to make HSCs successfully? Scientists can make blood cells from endothelial cells now and can monitor these in the embryo. But not all endothelial cells give rise to HSCs. The team used a special marker to follow the development of HSCs. Progenitor cells in the first wave of embryo blood-cell development and the HSCs of later waves of development differentiate from distinct populations of blood-producing endothelial cells. The marker, called Ly6a, is expressedin the endothelial cells that lead to HSCs, and it is not expressed in endothelial cells that make the first wave of blood cells.
Knowing more about the development of HSCs and its distinct markers will be helpful in making HSCs in the lab for stem-cell therapies so leukemia patients, for example – many of whom are unable to find suitable donors – could use their own cells to make HSCs and eventually blood cells depleted by blood cancers and some of its treatments.
The work was funded in part by the National Heart, Lung, and Blood Institute.
###
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.