In situ fate mapping identifies the neonatal origin of platelet-biased hematopoietic stem cells

However how these biased fate programs change through development remains poorly understood. Here, using single-cell lineage tracing, we map the function and state of thousands of individual mouse HSCs spanning from the earliest mature fetal stages until young adults.

We identify a burst of platelet- and myeloid-biased HSCs during the first postnatal week. Fetal HSCs retain a fetal-like program even after 4 months in the recipient bone marrow, suggesting that the adult HSC program is epigenetically configured early after birth. Creating a single-cell atlas of mouse perinatal HSCs, we identify a transient HSC state with hallmarks of Epithelial-Mesenchymal Transition (EMT), mTOR complex 1 activity, and cholesterol synthesis (SREBP targets).