Mapping the human heart, cell by cell

Date:
September 24, 2020
Source:
Howard Hughes Medical Institute
Summary:
Scientists have mapped and described the function of cells in six
regions of the adult heart, providing a new foundation for studying
heart disease.



FULL STORY ========================================================================== Ka-thump. Ka-thump. Ka-thump. Though we barely notice it most of
the time, the steady beating of a human heart is an amazingly complex performance. Like an orchestra, thousands of cells have to master their individual performances as well as work together.


==========================================================================
Now a team of scientists has created the first atlas of human heart
cells, a collection of maps showing nearly half a million heart cells and identifying the role of each in the heart's symphony. The researchers
examined six regions in 14 healthy donor hearts, creating a detailed
database that provides a new basis of comparison for studying heart
disease, the leading cause of death worldwide.

To understand what's going wrong in various forms of heart disease,
"first we need to know what is normal," says Howard Hughes Medical
Institute Investigator Christine Seidman, a cardiovascular geneticist
at Harvard University and director of the Cardiovascular Genetics Center
at Brigham and Women's Hospital.

Seidman and colleagues describe the new heart atlas September 24, 2020,
in the journal Nature.

"I can summarize my thoughts in one word: monumental," says cardiologist Douglas Mann of Washington University School of Medicine in St. Louis, who
was not involved in the study. "I think it's a really big accomplishment
and will be a tremendous source of reference for the field." Heart cells
have proven particularly difficult to study. Unlike some cancer cells and
other tissues, there are no heart cells that can be grown indefinitely
in the laboratory and studied. Instead, much cardiac research is done
using mice, whose hearts have important differences from human hearts.

And healthy human hearts can be hard to find (most are used in
transplants).

Seidman's team relied on those unusual instances in which healthy
hearts were rejected for transplantation and could be frozen for use
in research. First, the researchers used a high-throughput sequencing
method to define individual characteristics of every heart cell. They
then mapped those cells in six regions of 14 human hearts, seven from
men and seven from women. "For the first time, we have a zip code for
each cell to know what population it belongs to," Seidman says.

The team also analyzed heart cells' RNA levels using fluorescent markers
to glean molecular details of their function. Identifying not only where
cells are, but which proteins they're producing, will be a particular boon
for research, Mann says. For instance, by comparing cells in diseased
hearts to those in healthy hearts using the atlas, researchers might
pinpoint differences and target new therapies for heart disease.

Though the researchers studied a relatively small group of hearts
("fourteen people cannot replicate the world's population," Seidman
says), the new atlas revealed some biological surprises. The team found previously unknown cell diversity in various parts of the heart. They
also uncovered differences between the healthy hearts of males and
females; females had a greater proportion of heart muscle cells, called cardiomyocytes, than males. That warrants more research, Seidman says,
as those cells might hold clues to differences in heart disease between
the sexes.

Still, "what we see is striking heterogeneity -- in terms of the diverse
cell types that we now know make up the tissue of the human heart, and in
terms of the regional differences within the heart," says cardiologist
Hugh Watkins of Oxford University in England, who was not part of the
study team. "It's certainly a much more complicated organ than many might
have imagined!" The atlas is part of the Human Cell Atlas initiative, an effort funded by the Chan Zuckerberg Initiative to map all the cell types
in the human body. "It takes a big village to do this," Seidman says. Her
group worked with an international team of experts on everything from
heart surgery to computational biology in order to create the database
atlas. All of the data are available at http://www.heartcellatlas.org.

Next, Seidman and her colleagues hope to expand the atlas to a more
diverse population (the initial hearts were all from white donors). They
are also beginning to compare the proteins made in healthy heart cells
to those affected by heart disease.

"In due course, what we really want to know is how the different cell
types fit together at the microscopic and functional level," Watkins
says. "That's another ambitious goal, but the atlas provided here is an exciting start."

========================================================================== Story Source: Materials provided by Howard_Hughes_Medical_Institute. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Monika Litviňukova', Carlos Talavera-Lo'pez, Henrike Maatz,
Daniel
Reichart, Catherine L. Worth, Eric L. Lindberg, Masatoshi
Kanda, Krzysztof Polanski, Matthias Heinig, Michael Lee, Emily
R. Nadelmann, Kenny Roberts, Liz Tuck, Eirini S. Fasouli, Daniel
M. DeLaughter, Barbara McDonough, Hiroko Wakimoto, Joshua M. Gorham,
Sara Samari, Krishnaa T.

Mahbubani, Kourosh Saeb-Parsy, Giannino Patone, Joseph J. Boyle,
Hongbo Zhang, Hao Zhang, Anissa Viveiros, Gavin Y. Oudit, Omer
Bayraktar, J. G.

Seidman, Christine E. Seidman, Michela Noseda, Norbert Hubner,
Sarah A.

Teichmann. Cells of the adult human heart. Nature, 2020; DOI:
10.1038/ s41586-020-2797-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200924141522.htm

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