Stephen Quake: A Cellular Mystery: How Do Many Cell Types Arise From a Single Genome?

In this Presidential Lecture, Stephen Quake presents his team’s efforts to build comprehensive cell atlases using single-cell transcriptomics. He begins with a tribute to Jim Simons, then explains the central dogma of molecular biology and the challenge of understanding how one genome gives rise to many cell types. He traces the history of single-cell RNA sequencing, from early amplification methods to modern high-throughput microfluidics. The core of the talk focuses on the Tabula Sapiens atlas, comprising over 1 million cells from 24 tissues of the same donors. This atlas enables the molecular characterization of more than 400 cell types and reveals the expression patterns of all transcription factors in the human genome. Quake highlights both cell-type-specific and ubiquitously expressed transcription factors, many of which remain uncharacterized. He also discusses the Hayflick limit and aging, including studies on parabiosis. The talk concludes with reflections on the future of cell atlases and their potential to transform biology and medicine.