| First Author | Hoppe PS | Year | 2016 |
| Journal | Nature | Volume | 535 |
| Issue | 7611 | Pages | 299-302 |
| PubMed ID | 27411635 | Mgi Jnum | J:236311 |
| Mgi Id | MGI:5805723 | Doi | 10.1038/nature18320 |
| Citation | Hoppe PS, et al. (2016) Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios. Nature 535(7611):299-302 |
| abstractText | The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses. Alternative models of lineage choice therefore cannot be excluded. Here we use novel reporter mouse lines and live imaging for continuous single-cell long-term quantification of the transcription factors GATA1 and PU.1 (also known as SPI1). We analyse individual haematopoietic stem cells throughout differentiation into megakaryocytic-erythroid and granulocytic-monocytic lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates megakaryocytic-erythroid versus granulocytic-monocytic lineage decision-making. Rather, our findings suggest that these transcription factors are only executing and reinforcing lineage choice once made. These results challenge the current prevailing model of early myeloid lineage choice. |
