Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA322308 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multilineage communication regulates human liver bud self-organization from pluripotency II
| PRJNA380268 | ENA
Project description:Conventional 2-D differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. 3-D organoids generate complex organ-like tissues, however it is unclear how heterotypic interactions impact lineage identity. Here we use single-cell RNA-seq to reconstruct hepatocyte-like lineage progression from pluripotency in 2-D culture. We then derive 3-D liver bud (LB) organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during LB self-organization. We find that LB hepatoblasts differentiate towards hepatocyte fate, and in addition express epithelial migration signatures characteristic of organ budding. We identify hypoxia and inflammation signatures in endothelial and mesenchymal cells, which we suggest induce LB vasculogenesis. We use network analysis to predict autocrine and paracrine signaling in LBs, and show that VEGF crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals inter-lineage communication that is required for self-organization, and illuminates previously inaccessible aspects of human organ development and regeneration.
2017-02-08 | GSE81252 | GEO
Project description:Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
| PRJNA301104 | ENA
Project description:Conventional 2-D differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. 3-D organoids generate complex organ-like tissues, however it is unclear how heterotypic interactions impact lineage identity. Here we use single-cell RNA-seq to reconstruct hepatocyte-like lineage progression from pluripotency in 2-D culture. We then derive 3-D liver bud (LB) organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during LB development. We find that LB hepatoblasts diverge from the 2-D lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark 3-D LBs against fetal and adult human liver scRNA-seq data, and find a striking correspondence between the 3-D LB and fetal liver cells. We use a receptor-ligand pairing analysis and a high-throughput inhibitor assay to interrogate signaling in LBs, and show that VEGF crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.
2017-06-21 | GSE96981 | GEO
Project description:Alternative RNA splicing (AS) regulates proteome diversity, including isoform-specific expression of several pluripotency genes. Here, we integrated global gene expression and proteomic analyses and identified a molecular signature suggesting a central role for AS in maintaining human pluripotent stem cell (hPSC) self-renewal. We demonstrate the splicing factor SFRS2 is an OCT4 target gene required for pluripotency. SFRS2 regulates AS of the methyl-CpG-binding protein MBD2, whose isoforms play opposing roles in maintenance of, and reprogramming to, pluripotency. While both MDB2a and MBD2c are enriched at the OCT4 and NANOG promoters, MBD2a preferentially interacts with repressive NuRD chromatin remodeling factors and promotes hPSC differentiation, whereas overexpression of MBD2c enhances reprogramming of fibroblasts to pluripotency. The miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and MDB2a. These data suggest that OCT4, SFRS2, and MBD2 participate in a positive feedback loop, regulating proteome diversity complexity in support of hPSC self-renewal and reprogramming. We isolated RNA from human fibroblasts and human embryonic stem cells for hybridization to the Affymetrix gene expression microarrays.
2014-04-20 | E-GEOD-55678 | biostudies-arrayexpress
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
2023-10-19 | E-MTAB-12390 | biostudies-arrayexpress
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
2023-10-19 | E-MTAB-12389 | biostudies-arrayexpress
Project description:Embryonic stem cell (ESC) self-renewal and differentiation are governed by a broad-ranging regulatory network. Although the transcriptional regulatory mechanisms involved have been investigated extensively, post-transcriptional regulation is still poorly understood. Here we describe a critical role of the THO complex in ESC self-renewal and differentiation. We show that THO preferentially interacts with pluripotency gene transcripts through Thoc5, and is required for self-renewal at least in part by regulating their export and expression. During differentiation, THO loses its interaction with those transcripts due to reduced Thoc5 expression, leading to decreased expression of pluripotency proteins that facilitates exit from self-renewal. THO is also important for the establishment of pluripotency, as its depletion inhibits somatic cell reprogramming and blastocyst development. Together, our data indicate that THO regulates pluripotency gene mRNA export to control ESC self-renewal and differentiation, and therefore uncover a role for this aspect of post-transcriptional regulation in stem cell fate specification. mouse J1 cells were transfected with non-targeting (NT), Thoc2, and Thoc5 siRNAs. Total RNA was isolated 96 hours after transfection.
2013-11-30 | E-GEOD-51496 | biostudies-arrayexpress
Project description:Alternative RNA splicing (AS) regulates proteome diversity, including isoform-specific expression of several pluripotency genes. Here, we integrated global gene expression and proteomic analyses and identified a molecular signature suggesting a central role for AS in maintaining human pluripotent stem cell (hPSC) self-renewal. We demonstrate the splicing factor SFRS2 is an OCT4 target gene required for pluripotency. SFRS2 regulates AS of the methyl-CpG-binding protein MBD2, whose isoforms play opposing roles in maintenance of, and reprogramming to, pluripotency. While both MDB2a and MBD2c are enriched at the OCT4 and NANOG promoters, MBD2a preferentially interacts with repressive NuRD chromatin remodeling factors and promotes hPSC differentiation, whereas overexpression of MBD2c enhances reprogramming of fibroblasts to pluripotency. The miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and MDB2a. These data suggest that OCT4, SFRS2, and MBD2 participate in a positive feedback loop, regulating proteome diversity complexity in support of hPSC self-renewal and reprogramming.
2014-04-20 | GSE55678 | GEO
Project description:Embryonic stem cells (ESCs) cells run a self-renewal gene expression program, requiring the expression of certain transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs remains enigmatic. Here we show that Cohesin exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of the cohesin subunit Rad21 reveal an ESC specific cohesin binding pattern that is characterized by a CTCF independent colocalization of cohesin with pluripotency related transcription factors. Upon ESC differentiation, these binding sites disappear and instead new CTCF independent Rad21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of cohesin subunits causes expression changes that are reminiscent of the depletion of key pluripotency transcription factors, demonstrating the functional relevance of the cohesin - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin interacting proteins Stag1 and Wapl, further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-05-19 | E-GEOD-24030 | biostudies-arrayexpress