![]() ( b) Schematic of iTRAQ-based quantitative proteomic analysis. Cells at matched stages of differentiation were collected for RNA-seq ( n = 4 independent experiments) and proteomic ( n = 5 independent experiments) analyses. ( a) Fetal and adult-stage CD34 + HSPCs were differentiated into ProEs ex vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype.
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