血液中的干细胞和使用高通量的单细胞基因表达分析祖细胞转录调控网络的表征

Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors in 597 single primary blood stem ａnd progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, ａnd through comprehensive bioinformatic analysis reveal positively ａnd negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, G1 ａnd G1b. Validation using transcriptional ａnd transgenic assays conrmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between G1 ａnd G1b. Single-cell expression proling therefore identies network states ａnd allows reconstruction of network hierarchies involved in controlling stem cell fate choices, ａnd provides a blueprint for studying both normal development ａnd human disease.、