Gene expression changes induced by Elp1 deficiency during early myeloid differentiation [elp1]

Previous studies have primarily been based on freshly harvested grafts, permitting only limited control over cells prior to transplantation. Here we demonstrate the ability of in vitro expanded hematopoietic stem and progenitor cells (cHSPCs) to engraft in the myeloid niche of the brain, and effectively replace endogenous microglia both in vivo and in vitro.

Utilizing genetic editing of cHSPCs, we identify elongator acetyltransferase complex subunit 1 (Elp1; also known as Ikbkap; encoding for the protein IKAP) as an essential gene for the generation of cHSPC-derived myeloid cells (HDMCs). In accordance with its role as a subunit of the Elongator complex, loss of Elp1 in early-stage HDMCs led to upregulation of a gene module associated with the unfolded protein response.