AI Article Synopsis
- Bone marrow failure (BMF) in patients with Fanconi anemia (FA) is linked to faulty hematopoietic stem and progenitor cells (HSPCs), which are crucial for producing blood cells.
- Researchers conducted single-cell transcriptome profiling of HSPCs from FA patients and found high expressions of genes related to p53, TGF-β, and notably, MYC.
- Inhibiting MYC expression reduced the ability of FA HSPCs to proliferate and suggested that MYC may lead to increased DNA damage and diminished stem cell function, contributing to BMF symptoms in FA patients.
Article Abstract
Bone marrow failure (BMF) in Fanconi anemia (FA) patients results from dysfunctional hematopoietic stem and progenitor cells (HSPCs). To identify determinants of BMF, we performed single-cell transcriptome profiling of primary HSPCs from FA patients. In addition to overexpression of p53 and TGF-β pathway genes, we identified high levels of MYC expression. We correspondingly observed coexistence of distinct HSPC subpopulations expressing high levels of TP53 or MYC in FA bone marrow (BM). Inhibiting MYC expression with the BET bromodomain inhibitor (+)-JQ1 reduced the clonogenic potential of FA patient HSPCs but rescued physiological and genotoxic stress in HSPCs from FA mice, showing that MYC promotes proliferation while increasing DNA damage. MYC-high HSPCs showed significant downregulation of cell adhesion genes, consistent with enhanced egress of FA HSPCs from bone marrow to peripheral blood. We speculate that MYC overexpression impairs HSPC function in FA patients and contributes to exhaustion in FA bone marrow.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796920 | PMC |
| http://dx.doi.org/10.1016/j.stem.2020.09.004 | DOI Listing |
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