Hi there! Today’s highlight is focusing on a major question for the haematology community: what is causing blood stem cell heterogeneity? Please do not hesitate to let me know your thoughts in the comments here or on Twitter (@BioRugby)!
Highlight #2: Chromatin accessibility is the main source of heterogeneity in foetal haematopoiesis
We have a limited understanding of the haematopoiesis in the human foetus. Particularly, it is unclear whether stem cell differentiation depends on transcriptional priming (lineage-specific transcription factors) or a broader epigenetic one. This preprint delves into this question, presenting a single-cell resolution study of foetal human blood stem and progenitor cells. The authors analysed the transcriptome and the chromatin accessibility of over 8000 cells from different organs, confirming the high heterogeneity of the stem cell compartment. They inferred some differentiation trajectories, although the most-well know transcription factors were not consistently identified. In addition, the authors combined the datasets, and with the exception of the progenitors linked to red blood cells and platelets, they have been unable to unequivocally associate chromatin accessibility to defined transcriptional signatures. Therefore, they concluded that stem cells in the developing foetus are minimally primed towards differentiation, and this priming is not due to specific transcriptional programs associated to mature cell types. Finally, they compared different organs, confirming the higher cycling tendency of stem cells from foetal liver, compared to bone marrow. In the future, it will be interesting to garner a better understanding of the signals that trigger differences between haematopoietic sites.
Ranzoni AM, Tangherloni A et al. “Integrative Single-cell RNA-Seq and ATAC-Seq Analysis of Human Foetal Liver and Bone Marrow Haematopoiesis”