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Status |
Public on Jun 30, 2023 |
Title |
Decoding the pathogenesis of DBA by single-cell RNA-seq |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Ribosomal protein dysfunction leads to diverse human diseases, including Diamond-Blackfan anemia (DBA). Despite the ubiquitous need for ribosomes in all cell types, the mechanisms underlying ribosomopathies manifesting with tissue-specific defects are still incompletely understood. In this study, at single cell resolution, we characterized the transcriptomes of highly-purified erythroid progenitors isolated from bone marrow (BM) of DBA patients, including non-treatment (NT), glucocorticoids (GC)-responsive (GCR) and GC-non-responsive (GCNR) patients. We uncovered that, rather than cell cycle arrest at G1 phase, erythroid progenitors in NT patients were compulsively entering cell cycle of S-phase, which triggered replication stress and consequently activated P53 pathway. In contrast, the cell cycle was restrained with compromised proliferation in GCR patients, but not GCNR counterparts, via elevating IFN pathway. More importantly, the combinational treatment of DEX and IFN exhibit a synergistic effect on erythrocytes from GCNR patients. Therefore, the innate cell cycle characteristics of erythroid progenitors is ascribed to the erythroid lineage specific defects of DBA. Controlling the cell cycle progression by IFN signaling underlies the GC clinical efficacy and combinational therapy of DEX and IFN holds great promise for GCNR patients.
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Overall design |
We sorted human BFU-E and CFU-E cells using flow cytometry from human bone marrow(healthy control, DBA patients), and then performed a modified single cell tagged reverse transcription protocol.
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Contributor(s) |
Wang B, Wang C |
Citation missing |
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Submission date |
Jul 01, 2020 |
Last update date |
Jun 30, 2023 |
Contact name |
Chenchen Wang |
E-mail(s) |
wangchenchen@ihcams.ac.cn
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Organization name |
State key laboratory of Experimental Hematology
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Street address |
Nanjing Road 288
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City |
Tianjin |
State/province |
Tianjin |
ZIP/Postal code |
300041 |
Country |
China |
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Platforms (1) |
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Samples (1) |
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Relations |
BioProject |
PRJNA643492 |
SRA |
SRP269513 |
Supplementary file |
Size |
Download |
File type/resource |
GSE153618_RAW.tar |
14.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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