This SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesThe first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Specimen part
View SamplesLoss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGF members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
Smad2 and 3 transcription factors control muscle mass in adulthood.
Specimen part, Time
View SamplesSalivary glands are essential structures that secrete saliva to the oral cavity and maintain oral health. Development of salivary glands in mice and humans is controlled by mesenchymally expressed fibroblast growth factor-10 (FGF10). Using single cell RNA-seq atlas of the salivary gland and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5), but after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNAseq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos populations express the hallmark of ancient ionocyte signature Foxi1, Foxi2, Ascl3 and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized salivary gland ionocytes that are important for the ionic modification of saliva. In addition, they maintain FGF10-dependent glands homeostasis via communication with FGFR2b-expressing epithelial progenitor and myoepithelial cells Overall design: Comparison of Fgf10+ expressing cell mRNA profiles from submandibular glands of 7 day old pups and 60 days old mice in duplicate
A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.
Specimen part, Genotype, Subject
View SamplesOocyte maturation is accompanied by a transition from mRNA stability to instability. We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping, in mRNA destabilization during mouse oocyte maturation.
Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.
Specimen part
View SamplesExpression profiling of isolated populations of prepachytene spermatocytes (LP), pachytene spermatocytes (RP) and spermatids (ST) from PWD and B6 was performed to study the genome wide variation in gene expression between two mouse subspecies. To evaluate the transcriptional difference between B6 and PWD in during meiosis, we compared their transcriptomes in sorted populations of pre-pachytene primary spermatocytes (Leptonema, Zygotene and Pachytene), pachytene spermatocytes (Mid-late pachytene and diplotene) and spermatids.
No associated publication
Specimen part
View SamplesIn order to study the consequences of the loss of Icsbp expression in hematopoiesis Granulocyte-Monocyte Progenitors from bone marrow were isolated from Icsbp wild type and deficient mice by flow cytometry. Global gene expression was performed using Affymetrix gene chip technology.
No associated publication
No sample metadata fields
View SamplesWe aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Specimen part, Cell line
View SamplesWe describe a novel subset of CD8+ DCs in lymphoid organs of nave mice characterized by expression of the CX3CR1 chemokine receptor. CX3CR1+CD8+ DCs lack hallmarks of classical CD8+ DCs, including IL12 secretion, the capacity to cross-present antigen and their developmental independence of the transcriptional factor BatF3. Gene expression profiling showed that CX3CR1+CD8+ DCs resemble CD8- cDCs. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX3CR1+ CD8+ DCs. A PDC relationship of the cells is further supported by the fact that they harbor characteristic D-J immunoglobulin gene rearrangements and that development of CX3CR1+CD8+ DCs requires E2-2, the critical transcriptional regulator of PDCs. Thus, CX3CR1+ CD8+ DCs represent a unique DC subset, related to but distinct from PDCs.
CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells.
No sample metadata fields
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