A novel role for in primitive erythropoiesis.

Stem cell leukemia ( or ) and lymphoblastic leukemia 1 () encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq data of early embryos showed that primitive erythroid cells express both and Therefore, to determine whether can function in primitive erythropoiesis, we crossed conditional knockout mice with mice expressing a Cre recombinase under the control of the Epo receptor, active in erythroid progenitors. Embryos with 20% expression of from E9.5 survived to adulthood. However, mice with reduced expression of and absence of (double knockout; DKO) died at E10.5 because of progressive loss of erythropoiesis. Gene expression profiling of DKO yolk sacs revealed loss of and many of the known target genes of the SCL-GATA1 complex. ChIP-seq analyses in a human erythroleukemia cell line showed that LYL1 exclusively bound a small subset of SCL targets including Together, these data show for the first time that can maintain primitive erythropoiesis.