PDX1 Binding in human embryonic stem cell derived pancreatic progenitor cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Shawn Hoon
PROVIDER: E-GEOD-58686 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:PDX1 binds and regulates numerous genes involved in human pancreatic development but also binds hepatic genes Examination of PDX1 regulated genes in pancreatic derived cell types
2014-06-21 | E-GEOD-58685 | biostudies-arrayexpress
Project description:PDX1 binds and regulates numerous genes involved in human pancreatic development but also binds hepatic genes Total RNA was extracted from day 0, day 10 and day17 of differentiated HES3 cells. Comparisons were made for day 10 and day 17 to day 0.
2014-06-21 | E-GEOD-58665 | biostudies-arrayexpress
Project description:Human embryonic stem cells (HESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. Here, we show that combining a second related ligand, BMP4, in combination with Activin A yields 15 to 20% more DE as compared to Activin A alone. The addition of recombinant BMP4 accelerates the downregulation of pluripotency factors, particularly SOX2, and results in upregulation of endogenous BMP2 and BMP4, which in turn leads to elevated levels of phospho-SMAD1/5/8 over the next three days of differentiation. Combined Activin A and BMP4 treatment also leads to an increase in the expression of DE genes CXCR4, SOX17 and FOXA2 when compared to Activin A addition alone. Comparative microarray studies between DE cells harvested on day 3 of differentiation further reveal a novel set of genes upregulated in response to initial BMP4 exposure. Several of these, including APLNR, LRIG3, MCC and LZTS1, are expressed either in the mouse primitive streak, the site of DE formation, or in nascent DE itself. Thus, this synergism between Activin A and BMP4 during the in vitro differentiation of HESC into DE suggests a complex interplay between BMP and Activin/Nodal signaling during the in vivo allocation and expansion of the endoderm lineage. 3 biological replicates of 3-day ActivinA treated HES3 human stem cell culture were compared to 3-day ActivinA+Bmp4 treated HES3 human stem cell culture and observed for differential genes expression
2011-11-10 | E-GEOD-30630 | biostudies-arrayexpress
Project description:Analysis of genes enriched in MIXL1+ sorted cells during primitive streak induction identified Apelin receptor (APLNR), a highly conserved member of the G-protein coupled receptor family. Depending upon the growth factor conditions used for differentiation, APLNR+ cells identified both posterior mesodermal and anterior mesendodermal components of the primitive streak. APLNR+ cells isolated from mesodermal differentiated cultures were enriched in hematopoietic blast colony forming cells (Bl-CFCs) and the addition of Apelin peptide enhanced the frequency and growth of both hematopoietic colonies and hESC-derived endothelial cells. These studies identified APLNR as a marker of primitive streak-like cells differentiated from hESCs and defined a novel role for Apelin as a regulator of early human hematopoiesis.
2012-02-12 | E-MEXP-3380 | biostudies-arrayexpress
Project description:Bone morphogenetic protein (BMP) signaling is known to support differentiation of human embryonic stem cells (hESCs) into mesoderm and extraembryonic lineages, whereas other signaling pathways can largely influence this lineage specification. Here, we set out to reinvestigate the influence of ACTIVIN/NODAL and fibroblast growth factor (FGF) pathways on the lineage choices made by hESCs during BMP4-driven differentiation. We show that BMP activation, coupled with inhibition of both ACTIVIN/NODAL and FGF signaling, induces differentiation of hESCs, specifically to M-NM-2hCG hormone-secreting multinucleated syncytiotrophoblast and does not support induction of embryonic and extraembryonic lineages, extravillous trophoblast, and primitive endoderm. It has been previously reported that FGF2 can switch BMP4-induced hESC differentiation outcome to mesendoderm. Here, we show that FGF inhibition alone, or in combination with either ACTIVIN/NODAL inhibition or BMP activation, supports hESC differentiation to hCG-secreting syncytiotrophoblast. We show that the inhibition of the FGF pathway acts as a key in directing BMP4-mediated hESC differentiation to syncytiotrophoblast. Human embryonic Stem Cells (hESCs) were treated under defined conditions (N2B27) with BMP4 (B), SB431542 (SB) (ACTIVIN/NODAL inhibitor), SU5402 (SU) (FGFR1 inhibitor), FGF2 (F) either alone or in various combinations as mentioned, followed by isolation of total RNA.
2012-10-17 | E-GEOD-30125 | biostudies-arrayexpress
Project description:Here we performed the first combinatorial small molecule screen for the rapid conversion of hPSCs into postmitotic neurons. We identified a combination of five small molecule pathway inhibitors sufficient to yield neurons at > 75% efficiency within 10 days of differentiation in the absence of any recombinant growth factors. The resulting human neurons express canonical markers of nociceptive sensory fate. Two treatments (LSB and 3i) at days 2,3,5,7,9, and 15, in triplicate
2011-04-01 | E-GEOD-26867 | biostudies-arrayexpress
Project description:DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells (iPS cells) may reflect a âground stateâ upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells (ONS cells) are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation and movement, functions known to be affected in schizophrenia patient-derived cells. Only 5 gene loci were differentially methylated in all three cell types. These findings suggest that schizophrenia-associated DNA methylation may be a response to the homeostatic demands of different cell types in their local environments. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally-induced epigenetic regulation. This dataset represents the gene expression part of the study. The DNA methylation data is deposited under accession E-MTAB-2154.
2017-11-01 | E-MTAB-5016 | biostudies-arrayexpress
Project description:Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many of the potential applications are still limited by the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. These challenges could be overcome by the use of adult tissue stem cells derived from hPSCs, as their restricted potential could limit the differentiation towards other undesired linages, and allow in vitro expansion and long- term propagation of fully differentiated tissue. To isolate adult stem cells from hPSCs, we applied genome-editing to generate an LGR5-GFP reporter system and subsequently developed a differentiation protocol for human intestinal tissue comprising an adult stem cell niche and all major cell types of the adult intestine. This novel derivation protocol is highly robust and even permits the isolation of intestinal organoids without the LGR5 reporter. Transcriptional profiling, electron microscopy and functional analysis revealed that such human organoid cultures could be derived with high purity, and a composition and morphology similar to that of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. With our ability to genetically engineer hPSCs using site-specific nucleases, this adult stem cell system provides a novel platform by which to study human intestinal disease in vitro. RNA from primary organoid samples was isolated from organoid lines that were both cultured for 1-6 months and derived from duodenum, ileum, or rectum biopsies of human subjects as described previously (Sato et al., Gastroenterology 2011) grown in media called WENR+inhibitors. RNA was also isolated from various steps in the culturing and differentiation protocol.
2014-04-24 | E-GEOD-56930 | biostudies-arrayexpress
Project description:This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6 after inhibition of the Notch signaling pathway. Cochleas from postnatal day 0 and postnatal day 5 were cultured for 24 hours in the gamma secretase inhibitor DAPT or DMSO as a vehicle control. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 0+24 hours culture and postnatal day 5 + 24 hours culture. (corresponding to P1 and P6). mRNA profiles of P0 and P5 supporting cells (GFP+) and all other cochlear cell types (GFP-) treated with DAPT or DMSO, two replicates each, were generated by deep sequencing using Illumna TruSeq.
2016-07-01 | E-GEOD-83340 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-01 | E-GEOD-83357 | biostudies-arrayexpress