The Onset of Myeloid Differentiation in Hematopoietic Progenitors In Vivo is Coordinated with S-phase Progression
Greco, A.; Metz, J.; Frank, L.; Claudino, N.; Rodewald, H.-R.; Hofer, T.
Show abstract
Hematopoiesis produces diverse cell types in large quantities. How hematopoietic stem cells (HSCs) initiate lineage differentiation in vivo is not known. Here, we jointly measure chromatin accessibility and transcriptomes in single stem and progenitor cells and uncover a tight interplay between cell-cycle progression and the onset of differentiation. The cell cycle continuously accelerates as HSCs transition to uncommitted multipotent progenitors. In these uncommitted progenitors, proliferative activation is followed by the opening of myeloid-specific chromatin loci in S phase and, subsequently, myeloid gene expression. S phase-coupled onset of myeloid differentiation becomes quantitatively enhanced in emergency myelopoiesis. At the molecular level, we find that chromatin occupancy by HOXA9 - a key transcription factor of uncommitted progenitors - predicts whether the transition through S phase will initiate myelopoiesis, or whether the uncommitted progenitor state will be retained. Taken together, our findings provide a mechanistic framework for the onset of myeloid lineage differentiation in vivo.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Loss of PRC2 subunits primes lineage choice during exit of pluripotency 97%
- Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation 97%
- Mechanisms of Epigenomic and Functional Convergence Between Glucocorticoid and IL4-Driven Macrophage Programming 96%
Similar papers in this journal
Similar papers in this journal
- A mouse model with high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells 98%
- Synthetic enhancers reveal design principles of cell state specific regulatory elements in hematopoiesis 97%
- An engineered CRISPR/Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells 97%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.