Hematopoietic cells emerging from hemogenic endothelium exhibit lineage-specific oxidative stress responses

In this study, we sought to understand how low oxygen levels affect hematopoietic populations deriving from HE. We investigated the role of NRF2, glutathione metabolism and canonical/non-canonical TCA cycle pathways in specifying erythroid and non-erythroid populations. Here, we uncover striking differences in how oxidative stress affects and is dealt with by different hematopoietic populations following their emergence from HE. We performed a Multiome analysis with combined single-cell RNAseq and ATAC-seq on HE-derived populations following 72 hours of subculture at 4% O2 (termed hypoxia for simplicity) or ambient oxygen levels (normoxia). Samples are HE-derived cells cultured in hypoxia (H) or normoxia (N).