NFIX expression critically modulates early B lymphopoiesis and myelopoiesis

Keeshan, K. , O'Connor, C., Campos, J., Murphy, B., Hannon, M. and Michie, A. (2013) NFIX expression critically modulates early B lymphopoiesis and myelopoiesis. Experimental Hematology, 41(8), S68. (doi: 10.1016/j.exphem.2013.05.267)

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The commitment of stem and progenitor cells toward specific haematopoietic lineages is tightly controlled by a number of transcription factors that regulate a differentiation program via the expression of lineage restricting genes. Nuclear factor one (NFI, also known as NF-I, CTF (CAAT box transcription factor), Nuclear factor 1, NF-1) family of transcription factors (NFIA, NFIB, NFIC, and NFIX) act as transcriptional activators and/or repressors of cellular and viral genes and are documented to play a functional role in haematopoiesis, with NFIA being the most studied in this system. NFI protein family members act as homo- and heterodimers and bind promoters of genes expressed in different organs, including brain, lung, liver, intestine, muscle, connective tissue, skeletal elements and haematopoiesis. Data indicates that NFI proteins may act as tumor suppressor or oncogenes and putative drivers of lineage specification and perturbation. There has not been a described role for NFIX in lineage specificity in the haematopoietic system and we report here for the first time an important role of NFIX in B- and myeloid lineage differentiation. We investigated the function of NFIX during haematopoietic differentiation and demonstrate that NFIX represses the differentiation of pro-B cells and favors myeloid cell differentiation; thus it acts as a regulator of lineage specification in the haematopoietic system. NFIX is normally transcriptionally downregulated as B cells differentiate from Pro-B cells into immature and mature B cells and we show that NFIX overexpression in vivo blocks B cell development at the pro-B cell stage, and this correlates with transcriptional changes. Using in vitro differentiation assays NFIX was able to drive myeloid differentiation even under B cell specific culture conditions from the HSC but not from committed pro-B cells. These data highlight a novel role for NFIX transcription factor in haematopoiesis and in lineage specification.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Michie, Professor Alison and Keeshan, Dr Karen and Campos, Ms Joana and O'Connor, Ms Caitriona
Authors: Keeshan, K., O'Connor, C., Campos, J., Murphy, B., Hannon, M., and Michie, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Experimental Hematology

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