GSE120239
Kinetics of Adult hematopoietic stem cell differentiation in vivo
Adult hematopoiesis has been studied in terms of progenitor differentiation potentials,  whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing  of endogenous adult hematopoietic stem cells (HSC) with flow cytometry and single-cell  RNA sequencing to characterize early steps of hematopoietic differentiation in the  steady state. Labeled cells, comprising primarily long-term HSC and some short-term  HSC, produced megakaryocytic lineage progeny within one week, in a process that  required only 2-3 cell divisions. Erythroid and myeloid progeny emerged simultaneously  by 2 weeks, and included a progenitor population with expression features of both  lineages. Myeloid progenitors at this stage showed diversification into granulocytic,  monocytic and dendritic cell types, and rare intermediate cell states could be detected.  In contrast, lymphoid differentiation was virtually absent within the first 3 weeks of  tracing. These results show that continuous differentiation of HSC rapidly produces  major hematopoietic lineages and cell types, and reveal fundamental kinetic differences  between megakaryocytic, erythroid, myeloid and lymphoid differentiation. Overall design: We combined inducible lineage tracing  of endogenous adult hematopoietic stem cells (HSC) with flow cytometry and single-cell  RNA sequencing to characterize early steps of hematopoietic differentiation in the  steady state.