Unravelling Cell Cycle and Ontogeny Transcriptional Heterogeneity in Hematopoietic Stem Cells Through Integrated Single Cell RNA-Seq

During fetal development, hematopoietic stem cells (HSCs) undergo a remarkable expansion through a combination of rapid proliferation and high rates of self-renewal. In contrast, adult HSCs are characterized by long-term quiescence. Understanding of the molecular mechanisms underlying these ontogeny-dependent differences in cell cycle and self-renewal is hampered by marked heterogeneity within the HSC compartment, making it difficult to distinguish overlapping signatures in bulk transcriptional data. Advances in single cell genomics provide a new opportunity to tease apart different sources of gene expression heterogeneity, including those relating to cell cycle and self-renewal capability.