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Title: The Role of STRA13 in Hematopoiesis
Keywords: Stra13, hematopoiesis, HSC, stem cells, ageing, stress hematopoiesis
Issue Date: 23-Jan-2014
Citation: AVINASH GOVIND BAHIRVANI (2014-01-23). The Role of STRA13 in Hematopoiesis. ScholarBank@NUS Repository.
Abstract: Hematopoiesis is a tightly regulated process maintained by a small pool of hematopoietic stem cells (HSCs). Precise lifelong regulation of HSCs is important for self-renewal and differentiation into mature blood cells. Stra13/Sharp2/DEC1, a basic helix-loop-helix orange (bHLH-O) transcription factor plays important roles in cellular proliferation, differentiation and apoptosis. Previous studies have identified the importance of Stra13 function in maintaining homeostasis of T regulatory (Treg) cells as aged Stra13 knockout (KO) mice show defective T cell activation and exhibit a lymphoproliferative autoimmune disease. However, the role of Stra13 in hematopoiesis has not been studied so far. Our study demonstrates that Stra13 is highly expressed in early progenitors Lin- Sca1+c-Kit+ (LSK) cells and in the long term hematopoietic stem cells (LT-HSCs) /SLAM (CD150+CD48-) and its expression is downregulated in the differentiated progenitors. Moreover, Stra13 mRNA expression is elevated in the LSK progenitors in aged mice (22-24 months) compared with LSK fraction of young mice (2-3 months). Our analysis indicates that Stra13 is dispensable during steady state hematopoiesis. However, the LSK fraction of young Stra13 knockout mice is more sensitive to genotoxic stress. Moreover, aged Stra13 knockout mice show decreased percentages of SLAM+ and LSK fraction of the bone marrow and skewed progenitor levels. With the help of gene expression profiling studies, we have identified potential target genes that may potentiate the role of Stra13 in hematopoietic stem cell ageing and response to genotoxic stress. Our data uncovers a novel role of Stra13 in ageing and stress hematopoiesis.
Appears in Collections:Ph.D Theses (Open)

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