MAFB ChIPseq in Human EndoCBH2 cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Homo sapiens
SUBMITTER: Jean-Philippe Cartailler
PROVIDER: E-MTAB-8612 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:MafA and MafB transcription factors have been shown to be key regulators of insulin and glucagon transcription. MafB is essential for alpha and beta cell differentiation, as MafB deficient mice produced fewer insulin+ and glucagon+ cells during development, with MafA expressed in remaining insulin+ cells. In contrast, beta cell development was reported to be normal in a total MafA knock out, although the animals developed beta cell dysfunction and diabetes as adults. However, we have found that MafB expression is elevated during development and retained in adult insulin+ cells after conditional removal of MafA in the pancreas. These studies will evaluate the broader significance of these insulin and glucagon regulators in alpha and beta cell development and function. Our efforts will focus on determining if the concerted actions of MafA and MafB factors are significant to beta cell formation, and we specifically plan to: Determine how alpha and beta cell differentiation is affected in MafA/MafB compound mutant mice during pancreas development. cDNA microarray studies (pancchip 6.0) with wild type, MafAKO, MafB-/-, and MafAKOMafB-/- mutant E18.5 pancreata will be performed to comprehensively identify genes controlled by MafA and MafB in developing alpha and beta cells.
2014-11-04 | E-MTAB-3070 | biostudies-arrayexpress
Project description:Pancreatic Beta-cells are essential for regulating blood glucose levels. Much of our knowledge relating to human Beta-cell development and function has depended on rodent models, which have provided a blueprint to confirm important cellular features in humans. The advent of next generation sequencing studies, however, has highlighted discrepancies in Beta-cells which exist between mice and men. The precise contribution of such differences has not yet been fully appreciated. Numerous studies have identified MAFB to be present in human Beta-cells postnatally, while its expression is restricted to embryonic and neo-natal Beta-cells in mice. Conversely, the related transcription factor MAFA is only active in mature murine Beta-cells and notably, knockout of MAFB has minimal effect on murine Beta-cell development and function, in contrast to MAFA. Using CRISPR/Cas9-mediated gene editing, coupled with endocrine cell differentiation strategies, we dissect the contribution of MAFB to Beta-cell development and function specifically in humans. MAFB knockout hPSCs have normal pancreatic differentiation capacity up to the progenitor stage, but favor somatostatin- and pancreatic polypeptide–positive cells at the expense of insulin- and glucagon-producing cells during endocrine cell specification. Our results uncover a requirement for MAFB late in the human pancreatic developmental program and identify it as a distinguishing transcription factor within islet cell subtype specification. Taken together, the current study demonstrates that MAFB has synonymous functions in mice and human Alfa and Beta-cell specification and uncovers previously unappreciated roles in other pancreatic endocrine cell types, in particular Gamma-cells. We propose that under-appreciated differences in rodent versus human pancreatic islet biology may be alleviated by expanding genetic observations in animal models by utilizing hPSCs to better model human Beta-cell development and associated disease pathophysiology such as diabetes.
2020-03-23 | GSE145347 | GEO
Project description:Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet beta (β) cells, characterized by inappropriate production of other islet cell-enriched hormones. Here we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin (Gast)-positive cells generated under conditions of chronic hyperglycemia and obesity. A human b cell line deficient in MAFB, but not one lacking MAFA, also produced a gastrin (GAST)-positive gene expression pattern. In addition, GAST was detected in human T2D β cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repress GAST gene transcription. These results support a novel, species-specific role for MafA and MAFB in maintaining adult mouse and human β cell identity, respectively, by repressing expression of Gast/GAST and other non-b cell hormones.
2023-05-01 | GSE230728 | GEO
Project description:The transcription factor MafB plays an essential role in β-cell differentiation during the embryonic stage in rodents. Although MafB disappears from β-cells after birth, it has been reported that MafB can be evoked in β-cells and is involved in insulin+ β-cell number and islet architecture maintenance in adult mice under diabetic conditions. However, the underlying mechanism by which MafB protects β-cells remains unknown. To elucidate this, we performed RNA sequencing using an inducible diabetes model (A0BΔpanc mice) that we previously generated. We found that the deletion of Mafb can induce β-cell dedifferentiation, characterized by the upregulation of dedifferentiation markers, Slc5a10 and Cck, and several β-cell-disallowed genes; and the downregulation of mature β-cell markers, Slc2a2 and Ucn3. However, there is no re-expression of well-known progenitor cell markers, Foxo1 and Neurog3. Furtherly, the appearance of ALDH1A3+ cell and disappearance of UCN3+ cell also verify the β-cell de-differentiation state. Together, our results suggest that MafB can maintain β-cell identity under certain pathological conditions in adult mice, providing novel insight into the role of MafB in β-cell identity maintenance.
2022-06-24 | GSE200355 | GEO
Project description:To investigate the function of MAFB in the regulation of human beta cell identity and maturity, we established EndoCbH2 cell lines in which MAFB has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from bulkRNA-seq of 3 biological replicates.
2023-09-21 | GSE228992 | GEO
Project description:MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains.Although it is well known that MafB is specifically expressed in macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages. To investigate detail function of MafB in nonadherent macrophages, we performed microarray analysis. Macrophages were derived from day 14.5 fetal livers of mafB- /- and WT mice. Suspensions of single fetal liver cells were prepared by mechanical disruption . A total of 106 cells in suspension were centrifuged at 1,200 rpm for 5 min, and the cell pellet was resuspended in Dulbeccoâs modified Eagleâs medium supplemented with 10% fetal calf serum (heat inactivated), streptomycin and penicillin (100 units/ml), and macrophage colony-stimulating factor (M-CSF) (10 ng/ml) and then seeded either onto a nonadhesive dishes coated with hydrophilic polymers (Hydrocell; Cell Seed, Tokyo). The culture medium was not changed throughout the experiment. M-CSF (final concentration, 10 ng/ml) was added every day from day 4 onwards. One, 2, 4, and 6 days after seeding, the cells were harvested and analyzed by flow cytometry. After 6 day culture, macrophages of Mafb-/- and WT were use microarray analysis .
2010-02-27 | E-GEOD-20419 | biostudies-arrayexpress
Project description:The transcription factor MafB is essential for differentiation and foot process formation of podocytes. In order to identify the downstream targets of MafB, we analyzed the Mafb-deficient podocyte by RNA-seq. We found slit diaphragm-related protein (Nphs1, Magi2), Rho GTPase-activating protein (Arhgap24, Iqgap2) and podocyte-specific transcription factor (Tcf21) were significantly reduced in MafB cKO glomeruli. This indicates that one of these factors might be directly regulated by MafB to maintain its function in podocyte maintenance.
2021-08-03 | GSE96044 | GEO
Project description:MafB is a transcription factor acts as an important regulator of the development and differentiation of various organs and tissues. MafB is expressed in sertoli, leydig, and germ cells in adult mice testis. However, analysis of MafB cKO mice testis showed that MAFB is required for the initiation of the first spermatogenic wave but not the subsequent waves. We examined the transcriptome profile of MafB-cKO Sertoli cells during the first spermatogenic wave. Results of the down-regulated genes revealed that some genes are direct targets of MAFB since the presence of MARE sites in their promoters. Thus, they are candidates of maintaining MAFB function in sertoli cells.
2023-12-21 | GSE94725 | GEO
Project description:MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains.Although it is well known that MafB is specifically expressed in macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages. To investigate detail function of MafB in nonadherent macrophages, we performed microarray analysis.
2010-02-23 | GSE20419 | GEO
Project description:MafB is a member of the Maf family of bZip transcription factor and plays important roles in the developmental processes of various tissues, as well as in cell-type specific gene expression. MafB is expressed in differentiating keratinocytes in mice and is transcriptionally up-regulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation is partially impaired and the cornified layer is thinner. To gain insights into more detailed molecular mechanisms of MafB regulation of epidermal development, we performed microarray analysis of mRNAs isolated from dorsal skin epidermis of MafB-/- and wild-type mice at E18.5. Epidermis was separated from dorsal skin tissues of E18.5 mouse embryos (MafB-/- and WT) by Dispase (Life Technologies) treatment. Total RNA was isolated using Trizol reagent (Life Technologies), purified using an RNeasy mini kit (Qiagen), and subjected to microarray analysis.
2015-11-26 | E-GEOD-75388 | biostudies-arrayexpress