{"doi":"10.1038/nature18320","title":"Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios","abstract":"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.","journal":"Nature","year":2016,"id":10792,"datarank":0.8048964022532777,"base_score":5.365976015021851,"endowment":5.365976015021851,"self_citation_contribution":0.8048964022532777,"citation_network_contribution":0.0,"self_endowment_contribution":0.8048964022532777,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":213,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0474,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2016-07-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28745,"name":"Michael Schwarzfischer","orcid":null,"position":1,"is_corresponding":false},{"id":28746,"name":"Dirk Loeffler","orcid":"0000-0001-9870-0088","position":2,"is_corresponding":false},{"id":2685,"name":"Konstantinos D. 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