Filters
Technology
Platform
GSE13285
Mus musculus, Homo sapiens
1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Scl/Tal1 confers hemogenic competence and prevents cardiomyogenesis in embryonic endothelium. Here we show that Scl both directly activates a broad gene regulatory network required for hematopoietic stem/progenitor cell (HS/PC) development, and represses transcriptional regulators required for cardiogenesis. Cardiac repression occurs during a short developmental window through Scl binding to distant cardiac enhancers that harbor H3K4me1 at this stage. Scl binding to hematopoietic regulators extends throughout HS/PC and erythroid development and spreads from distant enhancers to promoters. Surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic versus cardiac specification and Scl binding to the majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors to facilitate HS/PC emergence from hemogenic endothelium. These results uncover a dual function for Scl in dictating hematopoietic versus cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.
Publication Title
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Endothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl-/- embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31+Pdgfr+ cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl-/- hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Sclfl/flRosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl-/- endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.
Publication Title
Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. To identify alternate regeneration pathways in the thymus, we performed an unbiased transcriptome analysis of the non-hematopoietic (CD45-) stromal cell compartment of the thymus, which is less sensitive to thymic damage compared to the CD45+ hematopoietic compartment.
Publication Title
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Description
Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver
Publication Title
Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
The goal was to identify genes targeted by miR-30a.
Publication Title
The microRNA-30 family is required for vertebrate hepatobiliary development.
Sample Metadata Fields
No sample metadata fields
View Samples