Elp1 is required for myeloid differentiation and brain repopulation.

A genome-scale screen of around 20,000 genetic perturbations in ex vivo-expanded cultured haematopoietic stem and progenitor cells (cHSPCs) identifies regulators of glia-induced myeloid differentiation and brain microglia repopulation after transplantation. Elp1 emerged as essential for generating myeloid cells, suppressing the unfolded protein response during myeloid specification, though not for maintaining them. The expanded-cHSPC platform makes large-scale genetic interrogation of brain myeloid biology tractable despite scarce primary HSPCs.