Yue, Y.

Despite substantial advances in our understanding of hematopoietic stem cell self-renewal and differentiation, the underlying mechanisms have remained elusive. Neutrophils are the primary and rapid responders during infections of innate immunity and can quickly generate an enormous number of mature neutrophils for immune defense. The underlying mechanisms have been investigated but still present conflicts. Our previous study clearly redefined progenitors and reformed the hierarchy of hematopoiesis. Here, we aim to reveal the underlying mechanisms and provide a new interpretation of immune phenomena. We describe the conversion of the cell cycle from differentiation to proliferation in peripheral hematopoiesis. The differentiation hematopoietic progenitor cells (HPCs) were maintained in cell cycle G1 phase, controlled by the DNA replication of cell cycle. DNA replication switched and controlled the progenitor status from differentiation to proliferation. Our study showed that the initial progenitors in adult peripheral blood exhibit self-renewal capabilities but absent after lineage commitment is completed during hematopoiesis. Furthermore, GATA2 and CSF3R were identified as the key transcription factors which determine the co-segregation among neutrophils and other lineages, deciphering the underlying molecular mechanisms. Neutrophil present the shortest differentiation trajectories in the hematopoietic hierarchy, which decide their role as rapid responders. Our results revealed the straightforward characterization of HPCs differentiation and proliferation activities, facilitating advancements in inflammation and disease treatment.