The human body contains 40 trillion cells. That's x100 more cells in your body than there are galaxies in the universe. You are a walking cellular multiverse.
Although your 40 trillion cells all have the same genome, your body actually contains over 200 different types of cell. Each cell type differentially expresses disparate proteins to enable unique emergent phenotypes. Your cells are differentiated.
Consider something as simple as your skin. It's not just made of 'skin cells'. Skin is not homocellular. The first 0.5 mm alone contains keratinocytes, melanocytes, dendritic cells, merkel cells, and lymphocytes. Tissues are heterocellular.
Heterocellularity allows tissues to achieve multiple phenotypes from a common genome. In your skin, keratinocytes form a barrier against the outside world, while your lymphocytes fight off infections. Same genotype, differentiated phenotypes.
Coordinating heterocellularity requires constant communication between different cell types. This is called 'heterocellular signaling' and it's essential for all metazoan life.
Heterocellular signalling is also frequently dysregulated in disease. Cancer, neurodegenerative disorders, and infectious disease all involve disrupted heterocellular signalling. If we want to combat these conditions, we need to understand how different cells communicate.
Despite the importance of heterocellular signalling, it's experimentally awkward to study.
For example, if you lyse heterocellular mixture of cells and measure the signals using traditional biochemical methods, it's impossible to tell which signal originated from which cell type. This technical limitation makes studying signalling polarity between two cells a laborious process.
As a result, most people just look at one cell type at time. It's easier. We've learnt a lot that way, but it does mean our understanding of cell-signalling has been experimentally biased towards homocellular models (see A) when biology is actually heterocellular (see B).
Fortunately, things are starting to change.
Over the past few years several nascent techniques have emerged that now enable systems biology analysis of heterocellular signalling. These techniques have facilitated pioneering studies of heterocellular signalling and described unique intercellular communication events.
I've curated some of these developments into a new review article for Trends in Biotechnology entitled "Systems Biology Analysis of Heterocellular Signaling".
The review discusses how physical, spatial, and isotopic cell-resolving methodologies are empowering unique studies of heterocellular signalling. If you're interested in studying how cells communicate, take a look.
