The brain is an extremely heterogeneous tissue. Within one small piece, there are neurons transmitting information, oligodendrocytes and astrocytes acting as support cells and microglia functioning as part of the immune system. Within the major classes of neurons, there are – depending on who you ask – hundreds to thousands of different subclasses. Knowing each neuron’s specific function is essential to our understanding of how these neurons perform different roles in behaviors and systems. In this interview, Andreas Pfenning – Associate Professor in the Computational Biology Department in the School of Computer Science and a member of the Neuroscience Institute at Carnegie Mellon University (CMU; PA, USA) – shares the experimental and computational techniques he’s using to investigate cell heterogeneity in the brain. Additionally, we learn about the targeted therapeutics he’s developing, what’s next for his research and what we can expect from the session he’s part of at ABRF 2026 (28–31 March; PA, USA). What techniques and technologies do you use to investigate cell heterogeneity in the brain? We can break this down into computational techniques and experimental techniques. In my lab, we really span and try to integrate both disciplines. On the experimental side, we started off using droplet-based sequencing methods to conduct single-nucleus RNA-seq. We used single-nucleus – as opposed to single-cell – because the neurons and cell subtypes of the brain are very different shapes and sizes; if you’re using droplet-based techniques, where you’re flowing cells through a microfluidic device, the cells of different shapes might…
