Highly detailed map of the human heart could guide personalized heart treatments
Scientists have created a detailed cellular and molecular
map of the healthy human heart to understand how this vital organ
functions and to shed light on what goes awry in cardiovascular diseasee.
The work, published in the journal Nature, was led by investigators at Harvard Medical School, Brigham and Women's
Hospital, the Wellcome Sanger Institute, Max Delbruck Center for Molecular
Medicine (MDC) in Germany, Imperial College London and their global collaborators.
The team analyzed almost a half million individual cells to build the most
extensive cell atlas of the human heart to date.
The atlas shows the huge diversity of cells and reveals
heart muscle cell types, cardiac protective immune cells and an intricate
network of blood vessels. It also predicts how the cells communicate to keep
the heart working.
The research is part of the Human Cell Atlas initiative to map every cell type
in the human body.
The new molecular and cellular knowledge of the heart promises to enable better
understanding of heart disease and guide the development of highly
individualized treatments.
The work also sets the stage for therapies based on regenerative medicine in
the future, the researchers said.
Over a lifetime, the average human heart delivers more than 2 billion
life-sustaining beats to the body. In doing so, it helps deliver oxygen and
nutrients to cells, tissues and organs and enables the removal of carbon
dioxide and waste products.
Each day, the heart beats around 100,000 times with a one-way flow through four
different chambers, varying speed with rest, exercise and stress. Every beat
requires an exquisitely complex but perfect synchronization across various
cells in different parts of heart.
When this complex coordination goes bad, it can result in cardiovascular
disease, the leading cause of death worldwide, killing an estimated 17.9
million people each year.
Detailing the molecular processes inside the
cells of a healthy heart is critical to understanding how things go awry in
heart disease. Such knowledge can lead to more precise, better treatment
strategies for various forms of cardiovascular illness.
"Millions of people are undergoing treatments for cardiovascular diseases.
Understanding the healthy heart will help us understand interactions between
cell types and cell states that can allow lifelong function and how these
differ in diseases," said study co-senior author Christine Seidman,
professor of medicine in the Blavatnik Institute at Harvard Medical School and
a cardiovascular geneticist at Brigham and Women's.
"Ultimately, these fundamental insights may suggest specific targets that
can lead to individualized therapies in the future, creating personalized
medicines for heart disease and improving the effectiveness of treatments for
each patient," Seidman said.
The team studied nearly 500,000 individual cells and cell nuclei from six
different regions of the heart obtained from 14 organ donors whose hearts were
healthy but unsuitable for transplantation.
Using a combination of single-cell analysis, machine learning and imaging
techniques, the team could see exactly which genes were switched on and off in
each cell.
The researchers discovered major differences in the cells in different areas of
the heart. They also observed that each area of the heart had specific subsets
of cells--a finding that points to different developmental origins and suggests
that these cells would respond differently to treatments.
"This project marks the beginning of new understandings into how the heart
is built from single cells, many with different cell states," said study
co-first author Daniel Reichart, research fellow in genetics at Harvard Medical
School.
"With knowledge of the regional differences throughout the heart, we can
begin to consider the effects of age, exercise and disease and help push the
field of cardiology toward the era of precision medicine," added Reichart.
"This is the first time anyone has looked at the single cells of the human
heart at this scale, which has only become possible with large-scale
single-cell sequencing," said Norbert Hubner, co-senior author and
professor at Max Delbruck Center for Molecular Medicine. "This study shows
the power of single-cell genomics and international collaboration," he
added.
"Knowledge of the full range of cardiac cells and their gene activity is a
fundamental necessity to understand how the heart functions and to start to
unravel how it responds to stress and disease," added Hubner.
As part of this study, the researchers also looked at blood vessels running
through the heart in unprecedented detail. The atlas showed how the cells in
these veins and arteries are adapted to the different pressures and locations
and how this could help researchers understand what goes wrong in blood vessels
during coronary heart disease.
"Our international effort provides an invaluable set of information to the
scientific community by illuminating the cellular and molecular details of
cardiac cells that work together to pump blood around the body," said
co-senior author Michela Noseda of Imperial College, London.
"We mapped the cardiac cells that can be potentially infected by
SARS-CoV-2 and found that specialized cells of the small blood vessels are also
virus targets. Our datasets are a goldmine of information to understand
subtleties of heart disease," she added.
The researchers also focused on understanding cardiac repair, looking at how
the immune cells interact and communicate with other cells in the healthy heart
and how this differs from skeletal muscle.
Further research will include investigating whether any heart cells could be
induced to repair themselves.
"This great collaborative effort is part of the global Human Cell Atlas
initiative to create a 'Google map' of the human body," said Sarah
Teichmann of the Wellcome Sanger Institute, co-senior author of the study and
co-chair of the Human Cell Atlas Organising Committee.
"Openly available to researchers worldwide, the Heart Cell Atlas is a
fantastic resource, which will lead to new understanding of heart health and
disease, new treatments and potentially even finding ways of regenerating
damaged heart tissue," she added.