Trompouki E, Bowman TV, Lawton LN, Fan ZP, Wu DC, DiBiase A, Martin CS, Cech JN, Sessa AK, Leblanc JL, Li P, Durand EM, Mosimann C, Heffner GC, Daley GQ, Paulson RF, Young RA, Zon LI. Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. Cell. 2011 Oct 28; 147(3):577-89.

Citation

Trompouki E, Bowman TV, Lawton LN, Fan ZP, Wu DC, DiBiase A, Martin CS, Cech JN, Sessa AK, Leblanc JL, Li P, Durand EM, Mosimann C, Heffner GC, Daley GQ, Paulson RF, Young RA, Zon LI. 2011. Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. Cell. 147(3):577-89. Pubmed: 22036566 DOI:10.1016/j.cell.2011.09.044

Abstract

BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.

Related Faculty

Leonard Zon, M.D.

Zon Lab

The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.