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1.  Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation 
Developmental Cell  2016;36(5):572-587.
Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development.
Graphical Abstract
•Comprehensive genome-scale resource for studying embryonic blood cell specification•Genome-scale definition of cis elements driving differential gene expression•A gene regulatory network model for hematopoiesis aiding reprogramming experiments•Analysis suggests a role for TEAD factors in hematopoietic specification
Goode, Obier, Vijayabaskar et al. isolate cells at six different stages of hematopoietic differentiation, starting from embryonic stem cells, and perform a comprehensive multi-omics analysis of this developmental pathway. The data identify regulators of hematopoietic specification and highlight the minimum requirements for the reprogramming of non-blood cells to blood.
PMCID: PMC4780867  PMID: 26923725
2.  Direct Reprogramming of Murine Fibroblasts to Hematopoietic Progenitor Cells 
Cell Reports  2014;9(5):1871-1884.
Recent reports have shown that somatic cells, under appropriate culture conditions, could be directly reprogrammed to cardiac, hepatic, or neuronal phenotype by lineage-specific transcription factors. In this study, we demonstrate that both embryonic and adult somatic fibroblasts can be efficiently reprogrammed to clonal multilineage hematopoietic progenitors by the ectopic expression of the transcription factors ERG, GATA2, LMO2, RUNX1c, and SCL. These reprogrammed cells were stably expanded on stromal cells and possessed short-term reconstitution ability in vivo. Loss of p53 function facilitated reprogramming to blood, and p53−/− reprogrammed cells efficiently generated erythroid, megakaryocytic, myeloid, and lymphoid lineages. Genome-wide analyses revealed that generation of hematopoietic progenitors was preceded by the appearance of hemogenic endothelial cells expressing endothelial and hematopoietic genes. Altogether, our findings suggest that direct reprogramming could represent a valid alternative approach to the differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) for disease modeling and autologous blood cell therapies.
Graphical Abstract
•ERG, GATA2, LMO2, RUNX1c, and SCL reprogram fibroblasts to blood•Reprogrammed fibroblasts have multilineage hematopoietic potential•Loss of p53 increases efficiency and multilineage potential of reprogrammed cells•Generation of blood progenitors is preceded by the appearance of hemogenic cells
Batta et al. demonstrate that murine fibroblasts are reprogrammed to hematopoietic progenitors, with erythroid, megakaryocyte, and myeloid potential, by ectopic expression of hematopoietic transcription factors. Reprogramming efficiency is increased by loss of p53 function, and generation of blood cells is preceded by the appearance of hemogenic endothelium.
PMCID: PMC4542300  PMID: 25466247
3.  EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors 
Tristetraprolin (TTP) is a key mediator of processes such as inflammation resolution, the inhibition of autoimmunity and in cancer. It carries out this role by the binding and degradation of mRNA transcripts, thereby decreasing their half-life. Transcripts modulated by TTP encode proteins such as cytokines, pro-inflammatory agents and immediate-early response proteins. TTP can also modulate neoplastic phenotypes in many cancers. TTP is induced and functionally regulated by a spectrum of both pro- and anti-inflammatory cytokines, mitogens and drugs in a MAPK-dependent manner. So far the contribution of p38 MAPK to the regulation of TTP expression and function has been best described.
Our results demonstrate the induction of the gene coding TTP (ZFP36) by EGF through the ERK1/2-dependent pathway and implicates the transcription factor ELK-1 in this process. We show that ELK-1 regulates ZFP36 expression by two mechanisms: by binding the ZFP36 promoter directly through ETS-binding site (+ 883 to +905 bp) and by inducing expression of EGR-1, which in turn increases ZFP36 expression through sequences located between -111 and -103 bp.
EGF activates TTP expression via ELK-1 and EGR-1 transcription factors.
PMCID: PMC3342124  PMID: 22433566

Results 1-3 (3)