Primed and ready: understanding lineage commitment through single cell analysis

•Cell fate decisions are made by individual stem/progenitor cells.•Population analysis masks functional and molecular heterogeneity in single cells.•Single cell analysis reveals multilineage priming in multipotential cells.•Priming reflects the competency of the cell to commit to multiple lineages.

Regulation of lineage commitment in multipotential cells is key to maintaining a balanced hematopoietic output throughout life while retaining the capacity to respond to stress and infection. Cell fate decisions are made by individual stem cells, but population-level analysis obscures the mechanics of cell fate choice by averaging the molecular and functional heterogeneity that exists even in the most highly purified stem cell populations. Therefore, single cell analysis of both molecular and cellular phenotypes is crucial to delineate and interrogate the process of lineage commitment. We review recent single cell expression profiling, imaging, and clonal tracking studies that have provided new insights into commitment, focusing on the hematopoietic system, and suggest how new technologies may illuminate our understanding of lineage commitment in the near future.