A Journey into the Secrets of Human Cells

We, as humans, are curious and strive to explore everything there is to know. We venture into space to unravel the vastness of the universe and construct specialized vehicles to delve into the depths of the ocean, uncovering the mysteries that lie beneath. Yet, there are still countless wonders and secrets waiting to be discovered within ourselves – within our own bodies.

Humans and all other living organisms are composed of the same fundamental building blocks – the cells. However, between different organisms and even within one organism, a multitude of different cell types coexist. These variances exist to meet distinct requirements and fulfill diverse tasks. Consider, for instance, the disparities between bone cells, which create our skeletons, and the cells in our lungs that enable respiration. However, even slight variations among cells within a specific tissue or an organ can potentially have significant, yet not fully comprehended, implications for proper bodily function. On average, a human body consists of 37.2 trillion cells.

To discover all the unknown mysteries in our cells, scientists from around the globe, spanning a variety of research fields, have united in their efforts to construct a comprehensive map of the cells within the human body, known as the Human Cell Atlas (HCA). Through the identification and characterization of each individual cell in terms of its type, composition, function, and position, the HCA endeavors to revolutionize our understanding of biology.

Each cell type will be assigned a unique "ID card" that contains its specific information due to comprehensive characterization. Furthermore, an actual map is being developed to illustrate the precise location of every cell type, not only within the entire body but also within individual organs and tissues. This groundbreaking approach provides a profound understanding of cellular functions and unveils the intricate relationships between different cells.

The completed atlas will provide high-resolution views of organs and tissues that have never been available before. Due to the high number of data sets and diversity of individuals included, the atlas aims to be fully representative of humanity as a whole, delivering benefits for communities all around the world. Achieving such a comprehensive dataset will only be possible through remarkable global efforts. Having been established in 2016, the HCA currently includes more than 3,000 consortium members, from 97 countries who are actively involved in the project. Seven years on, the first large organ atlases, built by combining the efforts of many labs, are now starting to emerge.

_{Credit: Broad Institute of MIT and Harvard}

In order to tackle this immense project and unveil the intricacies of cellular diversity, state-of-the-art technologies and artificial intelligence (AI)-based techniques are indispensable.

In the past decade, remarkable technological advancements have revolutionized our ability to explore the world of cells. Scientists can now analyze the composition of single, individual cells, allowing them to not only decipher the complexity of a specific organ but also to uncover the unique composition of every distinct cell type within that organ. This breakthrough provides an unprecedented level of detailed information, that can be extended to translational applications such as disease treatment, drug development, and diagnostics. It vividly illustrates the remarkable heterogeneity within larger organs, unraveling their complex tapestry of cellular diversity. The strides made in single-cell technologies yielded in an exponential rise in recorded datasets.

To effectively make sense of the ever-increasing abundance of generated data and to combine data sets from a large variety of individuals, robust computational work based on AI and machine learning is essential. Helmholtz Munich plays a leading role in providing vital data integration mapping approaches and related metrics. To identify biological insights across datasets, these approaches must overcome batch effects; undesired technical variations between datasets that arise due to slight variations in laboratory conditions, and the inherent differences in sample states. To address this challenge, currently available methods have to be adapted and tuned to the tissue or organ, that needs to be analyzed.

The research findings from the HCA have already made significant strides in clinical applications, revolutionizing our understanding of diseases. By identifying disease-associated cell types and altered cell states, the HCA has provided crucial insights into disease mechanisms, diagnostics, regenerative medicine, and precision medicine. Comparing healthy and diseased cells reveals distinct differences, not only helping to depict diagnostic criteria but also pinpointing explicit targets for the development of targeted therapies. Moreover, the HCA serves as a starting point for possibly even preventing diseases.

The impact of the HCA on medicine has been particularly evident during the COVID-19 pandemic. By analyzing data from millions of cells, researchers gained a comprehensive understanding of viral infection and the body's response at the single-cell level. This knowledge shed light on disease progression and provided valuable insights into virus entry points.

_{Credit: Human Cell Atlas}

In addition, the first integrated Human Lung Cell Atlas (HLCA) has the potential to have a significant impact on basic research in lung diseases in the coming years. The HLCA provides a reference map of cellular identities and functions in the lungs like never before. The atlas has already improved the understanding of the differences in lung health among cells and people. It allows for comparison between lung diseases and healthy lungs, as well as to compare various lung diseases with each other. Ongoing research aims to utilize these reference maps to enhance our comprehension of disease initiation, facilitate early diagnosis, and explore why people can experience similar diseases with varying outcomes. Current efforts to extend this reference with spatial methods will further enhance our understanding by placing these cell types within the context of tissue architecture and enabling the systematic deciphering of local cell communication programs. Ultimately, this not only speeds up disease understanding but also has profound impacts on further steps such as drug testing and development.

Latest update: November 2023.