As illustrated in Figure 4A, the effects of TFBS activities represented by plus or minus signs of RCs were mostly unchanged between cells but were inverted between DEGs. The strengths of TFBS activities increased markedly in ST-HSCs compared with LT-HSCs. We applied our method to 2 public RNA-seq datasets that represented sequential cell development and lineage commitment. This analysis showed that the results of cell-lineage commitment agreed with the propensity of the regulatory activities detected in HSCs, rather than with that of sequential cell development. Therefore, regulators that play similar or different roles in accordance with cellular contexts might be general features that underlie cell fate decisions. Overall, our results suggest that HSCs exhibit flexible and rapid responses to local needs by controlling TFs that are expressed at steady-state or low levels via a highly complex regulatory network. Further studies should consider the implications of these regulatory modes based on instructive and/or stochastic models of stem cell fate decisions. In the present study, we demonstrated that specific lineage-affiliated TFs formed a resultant set of transcriptional regulation, i.e., 24 differentially expressed TFs that contributed significantly to the model were modulated by other TFs that were not differentially expressed. These TFs include immediate early genes that induce an early genomic response related to HSC biology. If they become PF-03814735 dysfunctional, LT-HSCs may be primed to an erythroid/megakaryocytic lineage via pathways that are controlled by other TFs. In summary, we obtained novel transcriptome data and developed a computational method for promoter modeling. Our method can be applied easily to other biological systems. Using these approaches, we identified transcriptional regulation modes that provide insights into how HSCs determine their phenotype.Future works that overcome the limitations of the present study, such as the Auranofin inclusion of enhancer activities that appear to be important in hematopoiesis and the analysis of the influence of transcriptional heterogeneity at the single-cell level, which can be assayed using promising techniques, would refine our findings and advance our understanding of the kinetic and regulatory aspects of stem cell biology.