Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD006575
PROVIDER: PRJNA387402 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Organoid technology provides the possibility to culture human colontissue and patient-derived colorectal cancers (CRC) while maintainingall functional and phenotypic characteristics. Labeling of human colonstem cells (CoSCs), especially in normal and benign tumor organoids, ischallenging and therefore limits usability of multi-patient organoidlibraries for CoSC research. Here, we developed STAR (STem cell Ascl2Reporter), a minimal enhancer/promoter element that reportstranscriptional activity of ASCL2, a master regulator of LGR5+ CoSCfate. Among others via lentiviral infection, STAR minigene labels stemcells in normal as well as in multiple engineered and patient-derivedCRC organoids of different stage and genetic make-up. STAR revealed thatstem cell driven differentiation hierarchies and the capacity of cellfate plasticity (de-differentiation) are present at all stages of humanCRC development. The flexible and user-friendly nature of STARapplications in combination with organoid technology will facilitatebasic research on human adult stem cell biology.
2018-01-29 | PXD006575 | Pride
Project description:Organoid technology provides the possibility to culture human colon tissue and patient-derived colorectal cancers (CRC) while maintaining all functional and phenotypic characteristics. Labeling of human colon stem cells (CoSCs), especially in normal and benign tumor organoids, is challenging and therefore limits usability of multi-patient organoid libraries for CoSC research. Here, we developed STAR (STem cell Ascl2 Reporter), a minimal enhancer/promoter element that reports transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC fate. Among others via lentiviral infection, STAR minigene labels stem cells in normal as well as in multiple engineered and patient-derived CRC organoids of different stage and genetic make-up. STAR revealed that stem cell driven differentiation hierarchies and the capacity of cell fate plasticity (de-differentiation) are present at all stages of human CRC development. The flexible and user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research on human adult stem cell biology.
2018-01-29 | GSE99133 | GEO
Project description:Wnt signals control three functions of intestinal crypts: maintenance of Lgr5 stem cells, proliferation of transit-amplifying daughters and formation of Paneth cells. Here, we study how the Wnt effector β-catenin/Tcf4 cooperates with the Wnt-activated transcription factor Ascl2 to control a stem cell transcription program. DNA elements that are co-occupied and synergistically regulated by Ascl2 and Tcf4 specifically map to stem cell genes. In vitro, Tcf4-/- mini-guts are rescued by Ascl2 expression, while Ascl2-/- organoids are rescued by Wnt signaling. A direct auto-activatory loop leads to an on/off expression pattern of Ascl2 with a threshold that depends on the previous state. Wnt/R-spondin1 activates this loop. This mechanism interprets Wnt levels in crypts and translates this continuous signal into a discrete Ascl2 âonâ or âoffâ decision. In turn Ascl2, together with β-catenin/Tcf, activates stem cell genes. Thus, Ascl2 forms a transcriptional 'stemness switch' that is both Wnt-responsive and Wnt-dependent Examination of Tcf4, B-catenin and Ascl2 DNA occupancy in murine intestinal organoids and human colorectal cancer cell lines *** Original raw files unavailable due to loss during backup ***
2016-07-15 | E-GEOD-84456 | biostudies-arrayexpress
Project description:Wnt signals control three functions of intestinal crypts: maintenance of Lgr5 stem cells, proliferation of transit-amplifying daughters and formation of Paneth cells. Here, we study how the Wnt effector β-catenin/Tcf4 cooperates with the Wnt-activated transcription factor Ascl2 to control a stem cell transcription program. DNA elements that are co-occupied and synergistically regulated by Ascl2 and Tcf4 specifically map to stem cell genes. In vitro, Tcf4-/- mini-guts are rescued by Ascl2 expression, while Ascl2-/- organoids are rescued by Wnt signaling. A direct auto-activatory loop leads to an on/off expression pattern of Ascl2 with a threshold that depends on the previous state. Wnt/R-spondin1 activates this loop. This mechanism interprets Wnt levels in crypts and translates this continuous signal into a discrete Ascl2 “on” or “off” decision. In turn Ascl2, together with β-catenin/Tcf, activates stem cell genes. Thus, Ascl2 forms a transcriptional 'stemness switch' that is both Wnt-responsive and Wnt-dependent
2016-07-15 | GSE84456 | GEO
Project description:Wnt signals control three functions of intestinal crypts: maintenance of Lgr5 stem cells, proliferation of transit-amplifying daughters and formation of Paneth cells. Here, we study how the Wnt effector β-catenin/Tcf4 cooperates with the Wnt-activated transcription factor Ascl2 to control a stem cell transcription program. DNA elements that are co-occupied and synergistically regulated by Ascl2 and Tcf4 specifically map to stem cell genes. In vitro, Tcf4-/- mini-guts are rescued by Ascl2 expression, while Ascl2-/- organoids are rescued by Wnt signaling. A direct auto-activatory loop leads to an on/off expression pattern of Ascl2 with a threshold that depends on the previous state. Wnt/R-spondin1 activates this loop. This mechanism interprets Wnt levels in crypts and translates this continuous signal into a discrete Ascl2 “on” or “off” decision. In turn Ascl2, together with β-catenin/Tcf, activates stem cell genes. Thus, Ascl2 forms a transcriptional 'stemness switch' that is both Wnt-responsive and Wnt-dependent.
2014-12-31 | GSE57053 | GEO
Project description:Human engineered CRC organoids were equipped with the intestinal stem cell reporter STAR reflecting transcriptional activity of ASCL2. Successfully growing organoids display heterogeneous STAR expression and grow into big structures, while growth-compromised organoids stay small and are either entirely STAR-pos or STAR-neg.
2022-02-23 | GSE193248 | GEO
Project description:The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. Despite significant recent inroads, the full complement of Wnt target genes and the mechanisms of regulation remain incompletely understood. Here we identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its close neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition/physical contact of its own promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 expression. This feedforward regulatory loop controls stem cell-related gene expression and is highly amplified in colorectal cancer.
2016-06-09 | GSE69036 | GEO
Project description:Human engineered CRC organoids were equipped with the intestinal stem cell reporter STAR reflecting transcriptional activity of ASCL2. Bulk RNA-sequencing was performed on STAR+ and STAR- cells after 5 days and after 12 days.
2023-12-01 | GSE207070 | GEO
Project description:Human engineered CRC organoids were equipped with the intestinal stem cell reporter STAR reflecting transcriptional activity of ASCL2. Bulk ATAC-sequencing was performed on STAR populations after 5 days and after 12 days of plating single STAR+ or STAR- cells.
2023-12-01 | GSE207068 | GEO
Project description:Human engineered CRC organoids were equipped with the intestinal stem cell reporter STAR reflecting transcriptional activity of ASCL2. Bulk RNA-sequencing was performed on STAR populations after 5 days and after 12 days of plating single STAR+ or STAR- cells.
2023-12-01 | GSE207069 | GEO