Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation

Terminal erythroid differentiation (TED) is the maturation process of proerythroblasts into enucleated erythrocytes. Animal models are essential for studying red blood cell disorders.

We isolated erythroblasts at different TED stages from mouse bone marrow using FACS and performed integrated multi-omics analyses.

We developed a stage-specific transcriptome and proteome profile, enhancing murine TED databases. The most significant changes occurred during the transition from proerythroblasts to basophilic erythroblasts, characterized by immune function suppression and activation of erythroid processes. Global gene and protein expression dynamics showed that orthochromatic erythroblasts exit the cell cycle, with transcription cofactors histone deacetylase 1(HDAC1), histone deacetylase 2(HDAC2), and cell division control protein 6 homolog (CDC6), playing key roles in cell cycle regulation. Additionally, autophagy was initiated at the basophilic stage, indicated by increased autophagy-related gene (ATG) mRNA levels and activation of autophagy marker proteins like microtubule associated protein 1 light chain 3 beta (LC3-I), optineurin (OPTN), and ATGs, including Atg7, Atg4b, Atg3, and Atg2b.

Overall, we have generated a foundational murine transcriptome and proteome dataset, providing insights into the functional dynamics and regulatory mechanisms of terminal erythroid differentiation.