Biomedical subjects

Marianne L Seney

Publications and source records attributed to Marianne L Seney.

4 recordsLinked to original sources

PubMed2025

Model-based multifacet clustering with high-dimensional omics applications.

High-dimensional omics data often contain intricate and multifaceted information, resulting in the coexistence of multiple plausible sample partitions based on different subsets of selected features. Conventional clustering methods typically yield only one clustering solution, limiting their capacity to fully capture all facets of cluster structures in high-dimensional data. To address this challenge, we propose a model-based multifacet clustering (MFClust) method based on a mixture of Gaussian mixture models, where the former mixture achieves facet assignment for gene features and the latter mixture determines cluster assignment of samples. We demonstrate superior facet and cluster assignment accuracy of MFClust through simulation studies. The proposed method is applied to three transcriptomic applications from postmortem brain and lung disease studies. The result captures multifacet clustering structures associated with critical clinical variables and provides intriguing biological insights for further hypothesis generation and discovery.

Humans↗

PubMed2005

Sex differences in the location of immunochemically defined cell populations in the mouse preoptic area/anterior hypothalamus.

The preoptic area/anterior hypothalamus (POA/AH) is sexually dimorphic in many vertebrates. We have defined specific cell populations within the POA/AH using immunocytochemical markers for estrogen receptor beta (ERbeta) and the R1 subunit of the GABA(B) receptor (GABA(B)R1). Our previous finding of sex differences in cell migration in this region in embryonic day 15 mice led us to examine sex differences in the location or size of chemically identified cell groups. At embryonic day 17 (E17), cells containing immunoreactive (ir) ERbeta in females were located more dorsal and lateral than those in males. In contrast to this positional sex difference seen at E17, ERbeta expression at P0 and adulthood showed a sex difference in cell number and area of immunoreactivity with a higher expression of ERbeta in males than females. Furthermore, in animals that were genetically deprived of gonadal and adrenal hormones by virtue of a disrupted gene coding for steroidogenic factor 1, cells containing ir ERbeta followed a female phenotype for location at E17 and a female phenotype for number of ir cells at P0 regardless of genetic sex, suggesting that circulating hormones may be influencing cell position in the POA/AH. A second phenotypically identified cell group containing ir GABA(B)R1 also had a sex difference in cell positions at E17. Females expressed GABA(B)R1 in cells with a more dorsal position than in males. These results provide support for the suggestion that sex differences in cellular organization in the developing hypothalamus arise from sex differences in cell migration.

Age Factors↗

PubMed2004

Loss of steroidogenic factor 1 alters cellular topography in the mouse ventromedial nucleus of the hypothalamus.

Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1) exhibit marked structural abnormalities of the ventromedial nucleus of the hypothalamus (VMH). In this study, we sought to determine the molecular mechanisms underlying the VMH abnormalities. To trace SF-1-expressing neurons, we used a SF-1/enhanced green fluorescent protein (eGFP) transgene. Although the total numbers of eGFP-positive cells in wild-type (WT) and SF-1 KO mice were indistinguishable, cells that normally localize precisely within the VMH were scattered more diffusely in adjacent regions in SF-1 KO mice. This abnormal distribution is likely due to the loss of SF-1 expression in VMH neurons rather than secondary effects of deficient steroidogenesis, as redistribution also was seen in mice with a CNS-specific KO of SF-1. Thus, the absence of SF-1 alters the distribution of cells that normally form the VMH within the mediobasal hypothalamus. Consistent with this model, the hypothalamic expression patterns of the transcription factors islet-1 and nkx2.1 also were displaced in SF-1 KO mice. Independent of gene expression, birthdate analyses further suggested that cells with earlier birthdates were affected more severely by the loss of SF-1 than were later born cells. We conclude that the absence of SF-1 causes major changes in cellular arrangement within and around the developing VMH that result from altered cell migration.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Differential colocalization of Islet-1 and estrogen receptor alpha in the murine preoptic area and hypothalamus during development.

Estrogen receptor (ER) expression and regulation is vital to the correct functioning of the neuroendocrine brain. Islet-1 (Isl-1) is a LIM homeodomain-containing transcription factor that has been implicated in neuronal differentiation, is located in the hypothalamus, and can alter ER function in vitro. We have determined that Isl-1 is localized in several regions of the hypothalamus, including the ER rich areas of the ventromedial nucleus (VMH), the preoptic area, and the anterior hypothalamus. Using double-label immunocytochemistry, we examined the overlap between immunoreactive ERalpha and Isl-1 in these different hypothalamic brain regions. In the developing brain, almost 100% of VMH cells that contain immunoreactive ERalpha also contain Isl-1. However, in older animals, the percentage of double-label cells decreased below 70%. This change is due to a decrease in the number of cells containing Isl-1, because there was no difference in the number of ERalpha-containing cells. By contrast, in more anterior regions of the hypothalamus, cells containing both Isl-1 and ERalpha were less common, with the two populations adjacent to each other, rather than overlapping. These data suggest that, although Isl-1 and ERalpha can interact, they are not always found in the same cells and that regulation of ERalpha function is not under the same control in the VMH, preoptic area, and the anterior hypothalamus.

Age Factors↗