A cellular map of the human lung is now available

What exactly are we talking about?

No one today goes on a trip or an outing without "modeling" it first using one of the many online guides to choose a restaurant, a store, a school or a place to visit. Most of us can no longer do without this information. Why not transpose this approach to a better understanding of who we are, what keeps us healthy, or on the contrary, what makes us sick?

We all know that living beings are made of cells, which are the basic units of the living world. When observed under the microscope, these cells have very distinct shapes. How different are they from one another, and how can these differences be represented in a way that is easily processed by a computer? How can we distinguish between neurons involved in different functions? What are the differences between the different cells in our immune system that protect us against aggression? All these questions can be summarized in one basic question: how many different cells are needed to form a human being?

Dr. Pascal Barbry, Director of Research at the Institute of Molecular and Cellular Pharmacology (IPMC, CNRS, Université Côte d'Azur) and member of the  RespirERA Institute explains: "A few years ago, researchers thought that there were probably no more than a few hundred cell types. The combined progress of nanobiotechnology, DNA sequencing and bioinformatics has now made it possible to develop techniques for creating an ID card for each cell type in all human tissues. These technologies measure gene expression in each cell and make it possible to distinguish one cell from its neighbor. The idea of using these approaches to develop a cellular atlas of the human body quickly caught the attention of international consortia of researchers, who decided to map out our organs. And that is how the international Human Cell Atlas (HCA) consortium started."
For Professor Sylvie Leroy, pulmonologist at Nice University Hospital and member of RespirERA, “it seemed important for us that teams like ours, at the forefront of research in respiratory health, should get involved in the adventure and work on the respiratory aspects of the HCA". For that reason, her team and the team of Pascal Barbry joined the Human Lung Cell Atlas (HCLA) project from the very beginning.

According to Pascal Barbry, one of the four coordinators of the network of biologists working on the lung within the HCA, the work published in Nature Medicine represents the "first integrated and universal transcriptomic reference of the human lung at the single-cell level. In other words, it’s a catalog of all the cells that can be detected today in a human lung, whether it’s healthy or diseased.”
 

What is it for?

The lung is a complex organ in constant contact with the external environment. It is associated with common diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer, but also rare diseases such as interstitial pathologies and pulmonary arterial hypertension. Professor Charles Marquette, Head of the Pneumology, Thoracic Oncology and Allergology Department at Nice University Hospital and member of the RespirERA Institute, notes that "these diseases are becoming more widespread, and the morbidity and mortality associated with them is also increasing". For him, “it is essential to invest all our energy in understanding and preventing them and improving treatments for these diseases often linked with aging and the environment, but also with air pollution. The work published today will be very useful for the RespirERA Institute recently created in Nice".

Because of its structure, the lung is an organ that is deep, fragile and difficult to access. For IPMC researcher Dr Laure Emmanuelle Zaragosi, "complete ex-vivo mapping of this organ is in itself a major step forward. This international and collaborative work is providing the first complete description of the lung in a format that is entirely free and accessible to all. These data will help us better understand how each cell functions and interacts with its neighbors. They will allow us to compare healthy and sick subjects of different ages, sex, body mass index or ancestral origins."

The first atlas was based on samples from 486 individuals, including 107 healthy subjects. Some of the samples come from several French volunteers from the clinical team of Prs Leroy and Marquette at Nice University Hospital, and the CNRS research teams of Drs Zaragosi and Barbry. This work led to the identification of 61 different cell types, providing the first consensual annotation of the human lung.

From now on, any researcher or clinician will be able to cross-reference their data with those in the atlas, and interpret new observations more quickly. 

What prospects for tomorrow ?

This new map of the lung will rapidly allow doctors and researchers to approach disease in a new way. Cellular variations between individuals, and even within the lung of a single individual, can now be better measured and understood. This work also shows how some cells in the lung, although not very abundant, play an important role in diseases such as cystic fibrosis and lung cancer.
A better understanding of the essential biological processes at the cellular level will help us develop new screening and diagnostic tools, personalize treatments and model their ex-vivo effectiveness.
And since what is happening today with the lung can be transposed to all the other organs of the human body, this approach will create a whole new framework for increasing knowledge and offers many rich opportunities. 

Photo: Sylvie Leroy and Pascal Barbry (Nice University Hospital, Institute of Molecular and Cellular Pharmacology, 3IA Côte d'Azur, CNRS, Université Côte d'Azur, IHU RespirERA)

About Human Cell Atlas

Human Cell Atlas (HCA) is an international consortium that was formed to create reference maps of all human cells with the aim of providing a better understanding of human health, and diagnosing, monitoring and treating disease. HCA is expected to have an impact in biology and medicine by contributing to further discoveries and translational applications and paving the way for precision medicine.
The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, the HCA now has over 2,900 members from 94 countries around the world. https://www.humancellatlas.org
The Human Cell Atlas Lung Biological Network is a group of scientists collaborating to map cell types and states in the human airways. This group is coordinated by Pascal Barbry, Alexander Misharin, Martijn Nawijn and Jay Rajagopal.