Abstract
When human cord blood derived CD34+ cells are induced to differentiate in vitro, they undergo rapid and dynamic morphological and molecular transformation that are critical for the fate commitment. Using ATAC-seq and single-cell RNA sequencing, we detected two phases of this process. In the first phase, we observed that a rapid and widespread chromatin opening - that makes most of the gene promoters in the genome accessible - precedes a global upregulation of gene transcription and a concomitant increase in the cell-to-cell variability of gene expression. The second phase is marked by a slow chromatin closure that precedes an overall downregulation of gene transcription and the emergence of coherent expression profiles that characterize distinct cell subpopulations. We further showed that the accessibility of promoters has a crucial effect on whether transcription factor changes will lead to alterations in the expression of their target genes. Our observations are consistent with a model based on the spontaneous probabilistic organization of the cellular process of fate commitment.
Competing Interest Statement
The authors have declared no competing interest.