GSE125848
Chromatin remodeling mediated by ARID1A is indispensable for normal hematopoiesis in mice (human RNA-Seq)
ARID1A is a component of the mammalian SWI/SNF complex involved in chromatin remodeling. A functional SWI/SNF complex is required for diverse physiological processes including hematopoiesis, however, the precise role played by ARID1A in hematopoietic development is unclear. Here we utilize hematopoietic cell-specific deletion of Arid1a in mice to uncover its role during adult hematopoiesis. We demonstrate that ARID1A is essential for maintaining the frequency and function of hematopoietic stem cells and its loss impaired the differentiation of both myeloid and lymphoid lineages. ARID1A deficiency led to a global reduction in open chromatin and ensuing transcriptional changes affected key genes involved in hematopoietic development. We also observed that silencing of ARID1A affected ATRA-induced differentiation of NB4 cells, suggesting its role in granulocytic differentiation of human leukemic cells. Overall, our study provides a comprehensive elucidation of its function in hematopoiesis and establishes ARID1A as a major regulator of chromatin dynamics in hematopoietic cells. Overall design: RNA-sequencing of control (LacZ sg) and ARID1A-deficient (sg1 and sg5) NB4 cells. Cells were treated with doxycycline for 7 days.