Selective silencing rather than targeted activation of gene expression underlies fate choice in human hematopoietic stem cells.
Parmentier, R.; Moussy, A.; Chantalat, S.; Racine, L.; Ravi, S.; Gao, N. P.; Stockholm, D.; Corre, G.; Deleuze, J.-F.; Gunawan, R.; Paldi, A.
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When human cord blood derived CD34+ cells are induced to differentiate in vitro, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. Using ATAC-seq and single-cell RNA sequencing, we detected two phases in this process. In the first phase, we observed a rapid and global chromatin opening that makes most of the gene promoters in the genome accessible, followed by widespread 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 and a subsequent overall downregulation of gene transcription and emergence of coherent expression profiles corresponding to distinct cell subpopulations. These observations are consistent with a model based on the spontaneous probabilistic organization of the cellular process of fate commitment.
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