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Feed-forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

ABSTRACT: We compared transcriptomes of terminally differentiated mouse 3T3-L1 adipocytes [Series GSE14004] and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. We used HCA to determine mechanisms of AR regulation and activity in human adipocytes. We found that AR is regulated in a feed-forward fashion by glucocorticoids. Total RNA isolated from human subcutaneous preadipocytes differentiated for up to 14 days.

ORGANISM(S): Homo sapiens

SUBMITTER: Scott Ochsner

PROVIDER: E-GEOD-39342 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Feed-forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

Project description:We compared transcriptomes of terminally differentiated mouse 3T3-L1 adipocytes [Series GSE14004] and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. We used HCA to determine mechanisms of AR regulation and activity in human adipocytes. We found that AR is regulated in a feed-forward fashion by glucocorticoids.

2012-07-13 | GSE39342 | GEO

Single-cell RNA-seq of de-differentiated mammary adipocytes during lactation

Project description:Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα+ preadipocyte- and fibroblast-like cells during pregnancy, and remain de-differentiated during lactation. Upon weaning, de-differentiated fibroblasts proliferate and re-differentiate into adipocytes. In order to determine the molecular signature of these de-differentiated adipocytes in the mammary gland, we compared these cells with classical adipocytes. Using the AdipoChaser-mT/mG system, we pre-labeled mature adipocytes with GFP expression to characterize the features of these de-differentiated adipocytes (Figure 4A), and then purified CD31-/CD45-/PDGFRα+/Tomato+ and CD31-/CD45-/PDGFRα+/GFP+ cells from the stromal vascular fraction (SVF) of lactating mammary gland at the peak of lactation through FACS. Gene expression analyses showed that the CD31-/CD45-/PDGFRα+/Tomato+ cells were indeed enriched with Tomato expression, while the CD31-/CD45-/PDGFRα+/GFP+ cells were enriched with GFP expression (Figure 4C). We then collected CD31-/CD45-/PDGFRα+/GFP+ cells as single cells for subsequent single cell RNA-sequencing analysis (Figure 4D-G, Supplemental. Figure S1A-G). After the flow sorting and single cell RNA amplification, 26 CD31-/CD45-/PDGFRα+/GFP+ cells passed the quality control, and these cells were used for single-cell RNA-sequencing analysis. Due to technical difficulties in sorting single mature white adipocyte through flow cytometry, adipocytes differentiated from the immortalized murine-derived brown pre-adipocyte cell line were used as mature adipocyte control (Pradhan et al., 2017). Additionally, we also included population RNA-seq experiments, i.e. three mature white adipocyte samples, two GFP+, and six GFP- ones.

2018-06-17 | E-MTAB-6818 | biostudies-arrayexpress

In situ promoter capture Hi-C data of differentiated SGBS human preadipocytes (days 0, 2, 8 and 16 of differentiation to adipocytes) and iPSC-derived hypothalamic neurons (days 12, 16 and 27 of differentiation)

Project description:Human SGBS preadipocytes were differentiated into adipocytes, and human iPSCs were differentiated into hypothalamic neurons. Cells were collected for in situ promoter capture Hi-C [PMID: 29988018] at several differentiation stages. The differentiations were performed in one biological replicate, with two technical replicates (different wells of the differentiation that were also processed individually during library preparation). SGBS Day0: Represents the preadipocyte state. SGBS Day2: Represents immature adipocytes. SGBS Day8: Represents early mature adipocytes. SGBS Day16: Represents mature adipocytes. Hypothalamic Day 12: Represents early hypothalamic neurons. Hypothalamic Day 16: Represents mid hypothalamic neurons. Hypothalamic Day 27: Represents mature hypothalamic neurons.

2021-05-29 | E-MTAB-10488 | biostudies-arrayexpress

Homo sapiens

Project description:GW7647 and Rosiglitazone treated human differentiated adipocytes

| PRJNA116963 | ENA

Open chromatin profiling (ATAC-seq) of SGBS human preadipocytes (days 0, 2, 8 and 16 of differentiation to adipocytes) and iPSC-derived hypothalamic neurons (days 12, 16 and 27 of differentiation)

Project description:Human SGBS preadipocytes were differentiated into adipocytes, and human iPSCs were differentiated into hypothalamic neurons. Cells were collected for ATAC-seq at several differentiation stages. The differentiations were performed in one biological replicate, with two technical replicates (different wells of the differentiation that were also processed individually during library preparation). SGBS Day0: Represents the preadipocyte state. SGBS Day2: Represents immature adipocytes. SGBS Day8: Represents early mature adipocytes. SGBS Day16: Represents mature adipocytes. Hypothalamic Day 12: Represents early hypothalamic neurons. Hypothalamic Day 16: Represents mid hypothalamic neurons. Hypothalamic Day 27: Represents mature hypothalamic neurons.

2021-05-22 | E-MTAB-10462 | biostudies-arrayexpress

Noise propagation with interlinked feed-forward pathways.

Project description:Functionally similar pathways are often seen in biological systems, forming feed-forward controls. The robustness in network motifs such as feed-forward loops (FFLs) has been reported previously. In this work, we studied noise propagation in a development network that has multiple interlinked FFLs. A FFL has the potential of asymmetric noise-filtering (i.e., it works at either the "ON" or the "OFF" state in the target gene). With multiple, interlinked FFLs, we show that the propagated noises are largely filtered regardless of the states in the input genes. The noise-filtering property of an interlinked FFL can be largely derived from that of the individual FFLs, and with interlinked FFLs, it is possible to filter noises in both "ON" and "OFF" states in the output. We demonstrated the noise filtering effect in the developmental regulatory network of Caenorhabditis elegans that controls the timing of distal tip cell (DTC) migration. The roles of positive feedback loops involving blmp-1 and the degradation regulation of DRE-1 also studied. Our analyses allow for better inference from network structures to noise-filtering properties, and provide insights into the mechanisms behind the precise DTC migration controls in space and time.

| S-EPMC4814832 | biostudies-other

Feed-forward and feed-backward amplification model from cochlear cytoarchitecture: an interspecies comparison.

Project description:The high sensitivity and wide bandwidth of mammalian hearing are thought to derive from an active process involving the somatic and hair-bundle motility of the thousands of outer hair cells uniquely found in mammalian cochleae. To better understand this, a biophysical three-dimensional cochlear fluid model was developed for gerbil, chinchilla, cat, and human, featuring an active "push-pull" cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti and using the time-averaged Lagrangian method. Cochlear responses are simulated and compared with in vivo physiological measurements for the basilar membrane (BM) velocity, V(BM), frequency tuning of the BM vibration, and Q?? values representing the sharpness of the cochlear tuning curves. The V(BM) simulation results for gerbil and chinchilla are consistent with in vivo cochlea measurements. Simulated mechanical tuning curves based on maintaining a constant V(BM) value agree with neural-tuning threshold measurements better than those based on a constant displacement value, which implies that the inner hair cells are more sensitive to V(BM) than to BM displacement. The Q?? values of the V(BM) tuning curve agree well with those of cochlear neurons across species, and appear to be related in part to the width of the basilar membrane.

| S-EPMC3010833 | biostudies-other

Feed-forward regulation of phagocytosis by Entamoeba histolytica.

Project description:The parasitic protozoan Entamoeba histolytica is aptly named for its capacity to destroy host tissue. When E. histolytica trophozoites invade the lamina propria of a host colon, extracellular matrices are degraded while host cells are killed and phagocytosed. The ability of E. histolytica to phagocytose host cells correlates with virulence in vivo. In order to better understand the mechanism of phagocytosis, we used an E. histolytica Affymetrix microarray chip to measure the total gene expression of phagocytic and nonphagocytic subpopulations. Using paramagnetic beads coated with a known host ligand that stimulates phagocytosis, phagocytic and nonphagocytic amoebae from a single culture were purified. Microarray analysis of the subpopulations identified 121 genes with >2-fold higher expression in phagocytic than in nonphagocytic amoebae. Functional annotation identified genes encoding proteins involved in actin binding and cytoskeletal organization as highly enriched gene clusters. Post hoc analyses of selected genes showed that the gene expression profile identified in the microarray experiment did not exist prior to cell sorting but rather was stimulated through phagocytosis. Further, these expression profiles correlated with an increase in phagocytic ability, as E. histolytica cultures exposed to an initial stimulus of phagocytosis showed increased phagocytic ability upon a second stimulus. To our knowledge, this is the first description of such feed-forward regulation of gene expression and phagocytic ability in a phagocyte.

| S-EPMC3497417 | biostudies-literature

Identification of active microRNA/transcription factor feed-forward loops during human adipogenesis

Project description:This SuperSeries is composed of the following subset Series: GSE29182: Identification of active microRNA/transcription factor feed-forward loops during human adipogenesis (mRNA) GSE29185: Identification of active microRNA/transcription factor feed-forward loops during human adipogenesis (miRNA) Refer to individual Series

2011-12-20 | E-GEOD-29186 | biostudies-arrayexpress

Histological Chorioamnionitis Induces Differential Gene Expression in Human Cord Blood Mononuclear Leukocytes from Term Neonates

Project description:Human transcriptome array analysis of human cord blood mononuclear leokocytes from neonates exposed to histological chorioamnionitis and compared with healthy neonates Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. Exposure to HCA may have long-term consequences including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. Our objective was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates and identify key genes and pathways involved in HCA. We found several key genes differentially expressed with exposure to HCA. These transcriptomes included novel genes and pathways associated with exposure to HCA. The differential gene expression included the key genes regulating inflammatory, immune, respiratory and neurological pathways, which may contribute to disorders in those pathways in neonates exposed to HCA.

2019-04-05 | GSE120855 | GEO

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