3037 – MULTIOMICS OF HUMAN PRIMITIVE FETAL LIVER HEMATOPOIESIS AT SINGLE CELL RESOLUTION

The formation of our blood system is highly relevant for our understanding of congenital immune disorders and childhood leukemia. In the embryo, blood cells emerge in waves that overlap in time and space. Due to the diversity of the system, single cell assays are important to unravel heterogeneity. Here, human first trimester primitive fetal liver (FL) cells are investigated at single cell resolution using CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing), a combined immunophenotypic and transcriptional assay. The classical immunophenotypic surface markers used to define progenitors in adult, were investigated in the embryo and the molecular profile assessed. The surface markers CD90 and CD49F, used to define Hematopoietic stem cells (HSCs), were largely preserved in the embryo. Myeloid progenitors however, identified with FLT3 or CD123, were heterogeneous, due to the ubiquitous expression of these markers during development. Using a projection approach an adult Bone Marrow (BM) data set was directly compared to the FL cells. Progenitors with a lympho-myeloid signature were found to decrease with gestational age, whereas molecularly defined HSCs were relatively enriched in adult BM. Additionally, a fetal specific multipotent progenitor with erythromyeloid signature was identified, which may represent a transient erythromyeloid progenitor originating prior to definitive HSCs. Based on differently expressed genes between fetal and adult cells, a fetal core signature was identified and found to be enriched in subtypes of pediatric leukemia, that can originate in utero. Thus, our data is of relevance for future studies of paediatric blood disorders and highlights key immunophenotypic and transcriptional differences between fetal and adult blood progenitors.