PU.1 Mimic Synthetic Peptides Selectively Bind with GATA-1 and Allow c-Jun PU.1 Binding to Enhance Myelopoiesis

Hematopoietic stem cells' commitment to myelopoiesis builds immunity to prevent infection. This process is controlled through transcription factor, especially Purine rich box 1 (PU.1) protein, which plays a central role in regulating myelopoiesis. The β3/β4 region of PU.1 accommodates a coactivator transcription factor, c-Jun, to activate myelopoiesis. However, an erythroid transcription factor, GATA-1, competes with c-Jun for the β3/β4 region, abolishing myelopoiesis and promoting erythropoiesis. This competitive regulation decides the hematopoietic stem cells' commitment towards either erythroid or myeloid lineage.

Therefore, this study investigated the in vitro and in vivo effect of novel synthetic PU.1 β3/β4 mimic peptide analogs and peptide-loaded hydrophilic poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles.

The designed peptides significantly increase the expression of corresponding myeloid markers, specifically CD33 in vitro. However, the in vivo delivery of peptide-loaded PLGA nanoparticles, which have sustained release effect of peptides, increases 10.8% of granulocytes as compared to control.

The observations showed that the fabricated nanoparticles protected the loaded peptides from the harsh intracellular environment for a longer duration without causing any toxicity. These findings highlight the possibility to use these peptides and peptide-loaded nanoparticles to increase hematopoietic stem cell commitment to myeloid cells in case of opportunistic infection.