Recent technical advances permit metabolic profiling at the single-cell level but existing methods are destructive, making it difficult to link metabolic state to functional outcomes in vivo. Here we perform simultaneous enzyme/transporter expression and lineage tracing analysis (MetaFate) in single Hematopoietic Stem and Progenitor Cells (HSPCs), identifying a myeloid-biased progenitor compartment with distinct metabolic properties that expands to fuel emergency myelopoiesis. Importantly, we show that metabolism actively regulates immune-cell production, with overexpression of the glucose-6-phosphate dehydrogenase enzyme of the pentose phosphate pathway skewing MPP output from B-lymphocytes towards the myeloid lineages. Collectively, our data reveal the metabolic cues that instruct innate immune cell development and show that HSPC metabolism can be manipulated to alter the cellular composition of the immune system.

Invited by Julie Helft and Diana Passaro.