News Release
A digital illustration of a bone with colorful cells shaped like buildings within the bone.
Image by Emma Vidal.

PHILADELPHIA— While research has uncovered many details about how blood cells function within bone marrow, the work of other cells existing in that space remained a relative mystery. Now, researchers from the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) have published a “bone marrow atlas” in Cell that provides a first-of-its-kind, full view of all the cells existing within it, offering a better understanding of both healthy and diseased blood production.

“For the first time, we will have a comprehensive framework to view the full gene expression and spatial organization of bone marrow cells,” said senior study author Kai Tan, PhD, a professor of Pediatrics in the Perelman School of Medicine and an investigator in CHOP’s Center for Childhood Cancer Research. “Although our paper is foundational, we envision the atlas will be used to develop new diagnostic tests, identify new CAR-T or other therapeutic targets, and discover spatial biomarkers of disease.”

Bone marrow mostly consists of blood cells, however, a small percentage of non-blood cells may play an important role in conditions such as leukemia, other blood cancers, or bone marrow failure syndromes. Through the team’s efforts, researchers and doctors now have a much clearer picture of the functions of the rarer, but key, cells in the bone marrow such as stromal cells, bone cells, and endothelial (blood vessel) cells.

By using single-cell RNA sequencing, the researchers were able to capture the full gene expression profiles of tens of thousands of individual cells, uncovering the complete mix of cell types that make up an organ.

Through work aided by both an artificial intelligence technique called machine learning and painstaking hand-labeling of individual cells, the team was able to discern both that healthy bone marrow has very distinct spatial organization and stromal cells are more closely associated with blood-producing cells than previously understood.

As a result, researchers were able to create an encyclopedia cataloguing which of these rare non-blood cells produce factors known to be important in human blood production, which will help guide researchers to focus future studies.

“When applied to leukemia patient samples, these techniques identify the expansion of mesenchymal cells, a type of rare non-blood cell, at the cancer cell site in the bone marrow,” said the study’s co-senior author Ling Qin, PhD, a professor of Orthopedic Surgery at Penn Medicine. “This reveals a potential new direction for future disease treatment.”

The study is part of the broader Human BioMolecular Atlas Program (HuBMAP), which is comprised of 42 diverse research teams at universities across 14 states and four countries, funded by the National Institutes of Health (NIH). Researchers are collaborating to create the next generation of molecular analysis technologies and computational tools, which will allow researchers to create foundational tissue maps and construct a full map, or atlas, of the function and relationships among cells in the human body.

“Studies of this magnitude are only possible with monumental team efforts,” said Shovik Bandyopadhyay, PhD, a lead author of the study and a physician-scientist in-training in Tan’s lab. “With the collaboration of multiple institutions and scientific consortia, we were able to gain fundamental insight into the microscopic building blocks of the human body.”

Overall, the team is optimistic about the doors their techniques and research are opening.

“We are just beginning to scratch the surface of what’s possible,” Tan said. “Future research can build on our work, expediting bone marrow studies with the hope that one day these digital pathways will lead to healthcare breakthroughs in acute leukemia and other bone marrow disorders.”

This research was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under awards U54 HL156090 and U54HL165442 (to KT). Additional support includes National Institutes of Health of United States of America grants U2CCA233285 (to KT), R01AG069401 (to LQ), and P30AR069619 (to The University of Pennsylvania). MD was supported by NIH NIDDK T32DK007314. ShB was supported by NIH T32GM007170, T32 HL007439, and F30CA277965.

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.

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