SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors
Sayantani Sinha1, Shankha Subhra Chatterjee1, Mayukh Biswas1
1Stem Cell and Leukemia Laboratory, Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Translational Research Unit of Excellence (TRUE), Salt Lake, Kolkata 700091, West Bengal, India.
Experimental Hematology
|March 30, 2018
Summary
Acquired aplastic anemia (AA) involves bone marrow failure. This study found SWI/SNF chromatin remodeler loss in AA hematopoietic stem cells, suggesting a role beyond autoimmune destruction.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Acquired aplastic anemia (AA) is a bone marrow failure condition.
- Autoimmune destruction of hematopoietic stem cells (HSCs) is a known cause of AA.
- Somatic mutations alone do not fully explain AA pathophysiology.
Purpose of the Study:
- To investigate the role of SWI/SNF chromatin remodeling complex in acquired aplastic anemia.
- To analyze SWI/SNF subunit expression in human AA hematopoietic stem and progenitor cells (HSPCs).
- To differentiate SWI/SNF expression patterns in AA from other conditions like myelodysplastic syndromes (MDS) and aging.
Main Methods:
- Gene expression analysis of SWI/SNF subunits in human AA bone marrow CD34+ HSCs and HSPCs.
- Comparison of SWI/SNF expression between AA patients, normal individuals, MDS patients, and aged individuals.
- Analysis of specific SWI/SNF core components and other subunits.
Main Results:
- Significant loss of SWI/SNF core components SMARCC1, ARID1B, ACTL6A, and SMARCD1 was observed in AA HSPCs.
- Expression of SMARCA4, SMARCB1, SMARCD3, and DPF2 remained intact in AA.
- PBRM1, BRD7, and SMARCA2 were significantly upregulated in AA patients.
- SWI/SNF expression alterations were specific to AA, differing from MDS and aged HSPCs (except for SMARCD1 loss in MDS and ACTL6A in aged).
Conclusions:
- Loss of SWI/SNF chromatin remodeling complex function is evident in acquired aplastic anemia.
- Defective SWI/SNF regulation in AA HSPCs may contribute to bone marrow failure, independent of autoimmune destruction.
- Findings highlight SWI/SNF subunit expression heterogeneity in AA HSPCs, warranting further validation.
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