論文 - 詳細
| RRC ID | 77336 |
|---|---|
| 著者 | Karayel Ö, Xu P, Bludau I, Velan Bhoopalan S, Yao Y, Ana Rita FC, Santos A, Schulman BA, Alpi AF, Weiss MJ, Mann M. |
| タイトル | Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis. |
| ジャーナル | Mol Syst Biol |
| Abstract |
Human erythropoiesis is an exquisitely controlled multistep developmental process, and its dysregulation leads to numerous human diseases. Transcriptome and epigenome studies provided insights into system-wide regulation, but we currently lack a global mechanistic view on the dynamics of proteome and post-translational regulation coordinating erythroid maturation. We established a mass spectrometry (MS)-based proteomics workflow to quantify and dynamically track 7,400 proteins and 27,000 phosphorylation sites of five distinct maturation stages of in vitro reconstituted erythropoiesis of CD34+ HSPCs. Our data reveal developmental regulation through drastic proteome remodeling across stages of erythroid maturation encompassing most protein classes. This includes various orchestrated changes in solute carriers indicating adjustments to altered metabolic requirements. To define the distinct proteome of each maturation stage, we developed a computational deconvolution approach which revealed stage-specific marker proteins. The dynamic phosphoproteomes combined with a kinome-targeted CRISPR/Cas9 screen uncovered coordinated networks of erythropoietic kinases and pinpointed downregulation of c-Kit/MAPK signaling axis as key driver of maturation. Our system-wide view establishes the functional dynamic of complex phosphosignaling networks and regulation through proteome remodeling in erythropoiesis. |
| 巻・号 | 16(12) |
| ページ | e9813 |
| 公開日 | 2020-12-1 |
| DOI | 10.15252/msb.20209813 |
| PMID | 33259127 |
| PMC | PMC7706838 |
| MeSH | Biomarkers / metabolism CRISPR-Cas Systems / genetics Cell Differentiation / genetics Cell Line Erythropoiesis* Gene Ontology Humans Membrane Proteins / metabolism Phosphorylation Protein Kinases / metabolism Proteome / metabolism Proteomics* Reproducibility of Results Signal Transduction* |
| IF | 8.991 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 33 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |