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Identification of a gene which affects hematopoietic lineage commitment and differentiation

Williams, J.H., Beaumont, J.G., Daly, L.N., Chan, K., Ingley, E., Tilbrook, P.A. and Klinken, S.P. (1997) Identification of a gene which affects hematopoietic lineage commitment and differentiation. Australian Journal of Medical Science, 18 (4). p. 147.

Abstract

We used the technique of representational difference analysis to identify genes expressed by the Jmac2 monoblastoid cell line that were not expressed by the parental J2E erythroid line from which it spontaneously arose. In addition to two previously characterised macrophage specific molecules, three novel rnRNA species were isolated (Hematopoietic Lineage Switch (HLS) 2, 5 and 7). Expression of HLS 2 and 7 were restricted primarily to hematopoietic cell lines of an immature phenotype, whilst HLS 5 was more widely distributed. Expression of HLS 2 and HLS 7 were also regulated during IL-6 or LIF-induced differentiation of marine Ml monoblastoid cells to macrophages. Expression of HLS 2 decreased approximately 3-fold within 24 hours of stimulation before returning to approximately half the level found in unstimulated control cells. In contrast, expression of HLS 7 dropped to indétectable levels four days following stimulation, kinetics similar to those observed for the transcription factor SCI/Tall. To investigate the functional role of HLS 7 during hematopoietic lineage commitment and differentiation, retroviral vectors were used to express full length cDNAs encoding sense and antisense HLS 7 in various hematopoietic cell lines. Oveiexpiession of HLS 7 in the J2E erythroid line blocked their potential to further differentiate in response to erythropoietin, reduced expression of erythroid specific cell surface markers and induced a morphological change to resemble the Jmac2 monoblastoid line. Overexpression of HLS 7 in the 707 erythroid line inhibited their differentiation in response to DMSO, whilst reduced expression, with the antisense construct, enhanced their differentiation potential compared to wild type and vector only control cells. Preliminary results indicate that altering expression of HLS 7 has little or no effect on cytokine induced differentiation of Ml monoblastoid cells to macrophages. Similar experiments are planned to investigate the functions the two remaining novel molecules, HLS 2 and 5.

Publication Type: Journal Article
Publisher: Australian Institute of Medical Scientists
URI: http://researchrepository.murdoch.edu.au/id/eprint/39586
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