Previously we have shown significant differences in lactation performance, mammary gland histology and expression profiles of mammary transcriptome during peak-lactation (lactation day 9; L9) between the ordinary CBA/CaH (CBA) and the superior QSi5 strains of mice. In the present study, we compared mammary gland histology between CBA and QSi5 at mid-pregnancy (pregnancy day 12; P12). We assessed lactation performance during the first 8 days of lactation of the 13th - 14th generation of the Advanced Intercross Line (AIL) (CBA X QSi5) mice.
Identification of gene sets and pathways associated with lactation performance in mice.
Specimen part
View SamplesThroughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts.
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone.
Specimen part
View SamplesThe QSi5 inbred strain of mice was established from an outbred Quackenbush-Swiss strain by full-sib inbreeding and selection on the basis of increased litter size and shortened inter-litter interval in the Department of Veterinary Physiology (later REPROGEN) , University of Sydney (Holt et al., 2004). The strain has an average litter size of more than 13 pups, and females commonly nurse up to 18 pups with greater than 90% survival to weaning. Along with an increased body weight (BW), these traits are clearly indicative of enhanced lactation performance (Knight et al., 1986). Indeed lactation performance, assessed by a weigh-suckle-weigh method, was 3-fold greater in QSi5 mice than the CBA strain (Riley et al., 2006). In this study, we utilize the divergent phenotypes of QSi5 and CBA/CaH mice to identify genes associated with enhanced mammary gland capacity.
Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice.
No sample metadata fields
View SamplesTo identify the precise molecular mechanisms that could contribute to the increase in colon carcinogenesis, microarray gene expression analysis was performed on colon RNA isolated from 5-week-old VhlF/F and VhlIE, VhlIE/Apcmin/+ and VhlF/F/Apcmin/+ mice.
Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
No sample metadata fields
View SamplesZebrafish embryo were analyzed at 30 and 60 % epiboly for changes in transcriptome of wild-type and MTspg mutant embryos
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
No sample metadata fields
View SamplesThe main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Specimen part, Treatment
View SamplesTo explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the Tet-off tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo.
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Specimen part, Treatment
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