PHILADELPHIA, May 6, 2024 /PRNewswire/ -- Researchers at
Children's Hospital of Philadelphia (CHOP) and the Perelman School of
Medicine at the University of
Pennsylvania revealed a powerful new bone marrow atlas that
will offer the public a first-of-its-kind visual passport into the
spectrum of healthy and diseased blood production. The findings
were published today in the journal Cell.
Researchers offer a first-of-its-kind
visual passport into the spectrum of 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 in the Department of Pediatrics 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."
Although spearheaded by CHOP and Penn, the study is also part of the broader
Human BioMolecular Atlas Program (HuBMAP). The HuBMAP
consortium is comprised of 42 diverse research teams at
universities across 14 states and four countries and 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 an 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, 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."
Scientists have long theorized that while most bone marrow
consists of blood cells, a small percentage of non-blood cells may
play an important role in pediatric and adult bone marrow diseases
such as leukemia, myeloproliferative disorders, or bone marrow
failure syndromes. However, prior to this study, research was
challenging due to technical issues arising from the rarity and
fragility of these cells.
This paper is the first to overcome those limitations and
comprehensively profile adult human bone marrow using single-cell
RNA sequencing. The technique captures the full gene expression
profiles of tens of thousands of individual cells, uncovering the
complete mix of cell types that make up an organ.
In the study, researchers focused on bone marrow that regulates
important processes in blood cell development and immunity. They
captured at least nine subsets of non-hematopoietic cells,
including stromal cells, bone cells, and endothelial (blood vessel)
cells – at least three of which have not been previously reported
and that produced critical supportive factors. Researchers were
able to create an encyclopedia of which of these rare non-blood
cells produce factors known to be important in human blood
production, which will help researchers better understand which
cellular communication to focus future studies on.
Their findings underscore the increasingly pivotal role
technology plays in today's biomolecular research. The authors
created the estimated 800,000 cell spatial bone marrow atlas to
correspond with a transcriptional atlas by leveraging a
sophisticated new technique called CODEX along with machine
learning. This approach, along with painstaking manual annotation
of thousands of cells and structures, led them to discern that
healthy bone marrow has very distinct spatial organization and fat
cells are more closely associated with blood-producing cells than
previously understood.
"We are just beginning to scratch the surface of what's
possible," said Tan. "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."
Ling Qin, PhD, the other senior
author for this study, and a professor of Orthopedic Surgery
in the Perelman School of Medicine agreed and said she also sees
the research yielding lasting effects.
"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
Qin. "This reveals a potential new direction for future disease
treatment."
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.
Bandyopadhyay et al. "Mapping the Cellular Biogeography of Human
Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic
Imaging." Cell. Online May 6,
2024. DOI: 10.1016/j.cell.2024.04.013
About Children's Hospital of Philadelphia:
A non-profit, charitable organization, Children's Hospital of
Philadelphia was founded in 1855
as the nation's first pediatric hospital. Through its long-standing
commitment to providing exceptional patient care, training new
generations of pediatric healthcare professionals, and pioneering
major research initiatives, the hospital has fostered many
discoveries that have benefited children worldwide. Its pediatric
research program is among the largest in the country. The
institution has a well-established history of providing advanced
pediatric care close to home through its CHOP Care Network, which
includes more than 50 primary care practices, specialty care and
surgical centers, urgent care centers, and community hospital
alliances throughout Pennsylvania
and New Jersey, as well as the
Middleman Family Pavilion and its dedicated pediatric
emergency department in King of
Prussia. In addition, its unique family-centered care and
public service programs have brought Children's Hospital of
Philadelphia recognition as a
leading advocate for children and adolescents. For more
information, visit https://www.chop.edu.
Contact:
Jennifer Lee
Children's Hospital of Philadelphia
(267) 426-6084
leej41@chop.edu
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SOURCE Children’s Hospital of Philadelphia (CHOP) and the Perelman School of
Medicine at the University of
Pennsylvania