3176 – MULTIPOTENT RAG1 PROGENITORS EMERGE DIRECTLY FROM HEMOGENIC ENDOTHELIUM IN HUMAN PSC DERIVED HEMOPOIETIC ORGANOIDS

Abstract

Defining the ontogeny of the human adaptive immune system during early embryogenesis has implications for understanding childhood diseases including leukemias and autoimmune diseases. Using RAG1:GFP human pluripotent stem cell reporter lines, we examined human T-cell genesis from pluripotent stem cell derived hematopoietic organoids. Under conditions favouring T-cell development, RAG1+ cells progressively up regulated a cohort of recognised T-cell associated genes, arresting development at the CD4+CD8+ stage. However, sort and re-culture experiments showed that early RAG1+ cells also possessed B-cell, myeloid and erythroid potential. Moreover, RNAseq analysis of the early RAG1+ cells indicat..