Orphan Nuclear Receptors ERRα/γ are competence factors for somatic cell reprogramming
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE31704 | GEO | 2015/05/27
SECONDARY ACCESSION(S): PRJNA145619
REPOSITORIES: GEO
Similar Datasets
Project description:We report the expression profiles of the nuclear receptor family of transcription factors, known regulators of metabolism, during iPSC generation. Unique but overlapping expression patterns were found in iPSCs derived from adipose derived stem cells (ADSCs) and embryonic fibroblasts (human and mouse) that correlate with developmental transitions in the cell. Total RNA was obtained from human embryonic fibroblast IMR90 cells (IMR90s) untreated, transduced with GFP or with the four reprogramming factors (Oct4, Sox2, Klf4, c-Myc; OSKM) at day 5 of reprogramming.
2015-05-27 | E-GEOD-31704 | biostudies-arrayexpress
Project description:Estrogen Related Receptors (ERRs) are key regulators of energy homeostasis and play important role in the etiology of metabolic disorders, skeletal muscle related disorders, and neurodegenerative diseases. Among the three ERR isoforms, ERRα emerged as a potential drug target for metabolic and neurodegenerative diseases. Although ERRβ/γ selective agonist chemical tools have been identified, there are no chemical tools that effectively target ERRα agonism. We successfully engineered high affinity ERRα agonism into a chemical scaffold that displays selective ERRβ/γ agonist activity (GSK4716), providing novel ERRα/β/γ pan agonists that can be used as tools to probe the physiological roles of these nuclear receptors. We identified the structural requirements to enhance selectivity toward ERRα. Molecular modeling shows that our novel modulators have favorable binding modes in the LBP of ERRα and can induce conformational changes where Phe328 that originally occupies the pocket is dislocated to accommodate the ligands in a rather small cavity. The best agonists up-regulated the expression of target genes PGC-1α and PGC-1β, which are necessary to achieve maximal mitochondrial biogenesis. Moreover, they increased the mRNA levels of PDK4, which play an important role in energy homeostasis.
| S-EPMC9137328 | biostudies-literature
Project description:[1] Microarray analysis in the rat myocardial tissue: 124I-HIB transplanted MI model Vs. phosphate buffered saline (PBS) injected myocardial infarction (MI) model Vs. Sham operated model [2] Microarray analysis in the rat adipose derived stem cells: 124I-HIB-labeled ADSCs Vs. Unlabeled ADSCs [1] We investigated the change of gene expression profile in sham operated-, PBS injected- and 124I-HIB-labeled ADSCs transplanted myocardium in rat myocaridial infarction (MI) model. [2] We compared gene expression profile with 124I-HIB labeled ADSCs and unlabeled ADSCs in vitro.
2015-01-06 | E-GEOD-64692 | biostudies-arrayexpress
Project description:T cell functional differentiation is mediated by lineage-specific transcription factors. T helper 17 (Th17) has been recently identified as a distinct Th lineage mediating tissue inflammation. Retinoic acid receptor-related orphan receptor gamma (ROR gamma) was shown to regulate Th17 differentiation; ROR gamma deficiency, however, did not completely abolish Th17 cytokine expression. Here, we report Th17 cells highly expressed another related nuclear receptor, ROR alpha, induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3. Overexpression of ROR alpha promoted Th17 differentiation, possibly through the conserved noncoding sequence 2 in Il17-Il17f locus. ROR alpha deficiency resulted in reduced IL-17 expression in vitro and in vivo. Furthermore, ROR alpha and ROR gamma coexpression synergistically led to greater Th17 differentiation. Double deficiencies in ROR alpha and ROR gamma globally impaired Th17 generation and completely protected mice against experimental autoimmune encephalomyelitis. Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma.
| S-EPMC2587175 | biostudies-literature
Project description:Adipose tissue harbours a significant number of multipotent adult stem cells of mesenchymal origin known as adipose-derived stem cells (ADSCs). Broad differentiation potential and convenient accessibility of ADSCs make them an attractive source of adult mesenchymal stem cell for regenerative medicine and cell developmental plasticity research. Genome-wide microarray expression profiling was performed to identify genes deregulated during osteogenic differentiation of ADSCs to evaluate developmental plasticity of these cells. Dynamics of epigenetic modifications were analyzed in parallel and associated with the gene expression profile. Gene expression profile was analyzed in adipose-derived stem cells (ADSCs) differentiated into osteogenic lineage from 3 donors and compared to undifferentiated cells from the same donors.
2015-01-11 | E-GEOD-63754 | biostudies-arrayexpress
Project description:Recent researches identified the existence of adipose derived stem cells (ADSCs) in adipose tissue. Perivascular ADSCs (PV-ADSCs) locate around vasculatures and can differentiate into vascular lineages. However, the detailed cellular heterogeneity within PV-ADSCs has not been investigated. Therefore, we performed single-cell profiling of subcutaneous (S-) and perivascular (PV-) ADSCs from wild-type and obese mice. After referring to the clustering strategies from other ADSCs’ single-cell data, we provided a more comprehensive picture and trajectory, especially for PV-ADSCs. Both single-cell analysis and in vitro experiments revealed that S-ADSCs from obese mice had impaired abilities of cell migration and proliferation compared to wild-type S-ADSCs. PV-ADSCs have distinctively intrinsic properties. We uncovered 4 subpopulations of PV-ADSCs including Dpp4+, Col4a2+, Clec11a+ and Sult1e1+ cells. Notably, the differentiative function of PV-ADSCs towards vascular lineages was mainly attributed to the existence of Clec11a+ subpopulation, which highly expressed Mgp. The present study provided an integrative view of the ADSCs’ variance from the perspective of origins and obesity.
2022-02-23 | GSE172336 | GEO
Project description:Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource for regenerative medicine. However, genetic manipulation and difficult-to-manufacture strategies used in reprogramming limit their clinical applications. Here, we show pluripotency can be induced from mouse somatic cells by specific small-molecule compounds. The completely chemically-induced pluripotent stem cells (CiPSCs) can be stably maintained in embryonic stem cell (ESC) culture medium and resemble ESCs in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. These findings suggest that exogenous master genes are dispensable for cell fate reprogramming and pave the way for the clinical application of somatic reprogramming techniques. Chemicals' acronyms: V, VPA; C, CHIR; 6, 616452; T, tranylcypromine; F, FSK; Z, DZNep; P, PGE2; R, RG108; S, SRT1720; M, 2-Me-5HT; D, D4476; B, Sodium butyrate. To compare the global gene expression pofile of mouse embryonic fibroblasts (MEFs), mouse adult lung fibroblasts (MAFs), mouse neonatal fibroblasts (MNFs), adipose-derived stem cells (ADSCs), chemical induced pluripotent stem cells (CiPS), embryonic stem cells (ESCs) and OSKM-iPSCs. We profiled the mRNA expression of each sample by microarray (Mouse OneArray® v2, Phalanx). Different sample set was normalized for different purpose. Set1: MEFs1, CiPS34, MNF CIPS7, CiPS50 CiPS21, OSKM-iPS1 and ESCs1 were analyzed, each sample have three replicates; Set2: MNFs, MAFs, ADSCs, MNF CiPS1, MAF CiPS3, CiPS45, ADSC CiPS2, OSKM iPS2 and ESCs2 were analyzed, each sample have three replicates; Set3: WT MEFs, ESCs3, CiPS WT1 and CiPS WT2 were analyzed, each sample have two replicates; Set4: MEFs2, SKM-FSK1, SKM-FSK2 and ESCs4 were analyzed, each sample have three replicates; Set5: MEFs3, ESCs5, CiPSCs, D12, D20 and D32 were analyzed, each sample have two replicates.
2013-07-22 | E-GEOD-48201 | biostudies-arrayexpress
Project description:Adipose-derived stem cells are angiogenic and attractive for therapeutic angiogenesis. However, ADSCs contain several subsets according to expression pattern of surface markers. We identified CD271 (LNGFR) can isolate ADSCs with superior capacity for angiogenesis. Therefore, we aimed to compare gene expression profile between CD271+ and CD271- ADSCs.
2019-01-14 | GSE125012 | GEO
Project description:Retinoic acid-related orphan receptors RORα and RORγ play a regulatory role in lipid/glucose homeostasis and various immune functions, and have been implicated in metabolic syndrome and several inflammatory diseases. RORα-deficient mice are protected against age- and diet-induced obesity, hepatosteatosis, and insulin resistance. The resistance to hepatosteatosis in RORα-deficient mice is related to the reduced expression of several genes regulating lipid synthesis, transport, and storage. Adipose tissue-associated inflammation, which plays a critical role in the development of insulin resistance, is considerably diminished in RORα-deficient mice as indicated by the reduced infiltration of M1 macrophages and decreased expression of many proinflammatory genes. Deficiency in RORγ also protects against diet-induced insulin resistance by a mechanism that appears different from that in RORα deficiency. Recent studies indicated that RORs provide an important link between the circadian clock machinery and its regulation of metabolic genes and metabolic syndrome. As ligand-dependent transcription factors, RORs may provide novel therapeutic targets in the management of obesity and associated metabolic diseases, including hepatosteatosis, adipose tissue-associated inflammation, and insulin resistance.
| S-EPMC3555121 | biostudies-literature