Single-cell analyses demonstrate that a heme-GATA1 feedback loop regulates red cell differentiation.

ABSTRACT: Erythropoiesis is the complex, dynamic, and tightly regulated process that generates all mature red blood cells. To understand this process, we mapped the developmental trajectories of progenitors from wild-type, erythropoietin-treated, and Flvcr1-deleted mice at single-cell resolution. Importantly, we linked the quantity of each cell's surface proteins to its total transcriptome, which is a novel method. Deletion of Flvcr1 results in high levels of intracellular heme, allowing us to identify heme-regulated circuitry. Our studies demonstrate that in early erythroid cells (CD71⁺Ter119^neg-lo), heme increases ribosomal protein transcripts, suggesting that heme, in addition to upregulating globin transcription and translation, guarantees ample ribosomes for

SUBMITTER: Doty RT 

PROVIDER: S-EPMC6356983 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature