ATF4 marks quiescent reserve cells of gastric chief cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA882403 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21639769_1.fastq.gz | Fastqsanger.gz | |||
| SRR21639769_2.fastq.gz | Fastqsanger.gz | |||
| SRR21639770_1.fastq.gz | Fastqsanger.gz | |||
| SRR21639770_2.fastq.gz | Fastqsanger.gz | |||
| SRR21639771_1.fastq.gz | Fastqsanger.gz |
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Project description:Hierarchically organized tissues, such as hematopoietic systems, muscle, or skin harbor deeply quiescent stem cells which start proliferating in response to external insults. In contrast, it remains obscure whether similar quiescent cells exist in epithelia of digestive organs. Here we identified a deeply quiescent population in gastric corpus but not in other gastrointestinal organs after systematic examination of H2b-GFP label-retaining cells. The label-retaining cells in corpus epithelia belonged to a subpopulation of chief cells that were located near basal layers of corpus and did not overlap with Troyhigh, Lgr5high, or Misthigh cell population. The identified quiescent cells were marked with activation of Atf4 and unfolded protein response. External damages by indomethacin treatment triggered proliferation of the quiescent populations, indicating that chief cells of gastric corpus harbor deeply quiescent reserve cells with high levels of internal stress response activity.
2023-10-31 | GSE213755 | GEO
Project description:Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4+ population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.
| S-EPMC10662433 | biostudies-literature
Project description:Adult stem cells residing within tubular glands of the corpus epithelium are believed to fuel daily tissue renewal, but their identity remains controversial. Lgr5, marks both homeostatic stem cells and “reserve” stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a new, non-variegated Lgr5-2A-CreERT2 mouse model, we show by cell fate mapping that Lgr5-expressing chief cells do not behave as corpus stem cells under homeostatic conditions, but are recruited to function as stem cells to effect epithelial renewal following injury. In vivo ablation of the Lgr5+ cells severely impairs epithelial homeostasis in the corpus, indicating an essential role in maintaining the resident stem cell pool. We additionally define the Lgr5+ chief cells as a major cell of origin of gastric metaplasia. These findings reveal clinically relevant insights into tissue homeostasis, repair and cancer in the corpus.
2017-05-01 | GSE86603 | GEO
Project description:Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bi-directionally towards pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of chief cells. By lineage tracing using a Troy-eGFP-ires-CreERT2 allele, single marked cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific, 'plastic' subset of differentiated chief cells capable of replenishing entire gastric units, essentially serving as a quiescent ‘reserve’ stem cell.
2013-10-23 | GSE44060 | GEO
Project description:The purpose of this single cell experiment is to compare and characterize at molecular level actively cycling stem cells in the isthmus and quiescent stem cells in the base of the mouse stomach corpus. The lineage tracing data from Stmn1-CreERT2 shows that Stmn1+ cells in the corpus isthmus include fast dividing isthmus stem cells with long-term potency. On the other hand, chief cells including Lgr5+ subpopulation can play as quiescent stem cells in the base that are largely quiescent in homeostasis, but are activated upon injury. The isthmus stem cells and chief cells are isolated by Stmn1 and Pgc, respectively, and were subject to single cell RNA-seq experiment.
2019-08-14 | E-MTAB-6879 | biostudies-arrayexpress
Project description:Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bi-directionally towards pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of chief cells. By lineage tracing using a Troy-eGFP-ires-CreERT2 allele, single marked cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific, 'plastic' subset of differentiated chief cells capable of replenishing entire gastric units, essentially serving as a quiescent ‘reserve’ stem cell. An EGFP-ires-CreERT2 cassette was introduced into the transcriptional start side of Tnfrsf19 (Troy), resulting in the expression of EGFP and CreERT2 under the control of endogenous Troy-regulatory sequences. Troy is expressed in basally located chief and parietal cells. Using FACS, Troy positive chief and parietal cells can be isolated separately. Expression profiling was performed on these two cell types: three arrays of sorted chief cells, two arrays of sorted parietal cells. As a reference, two arrays of separately isolated whole gastric corpus glands were added. In addition, single sorted Troy positive chief cells can be placed in culture, forming 3D cultures called organoids. Three arrays were generated from different organoid cultures, one time in normal medium containing the factors EGF, Gastrin, FGF10, Noggin, Wnt3a and Rspondin (EGFNWR medium) and one time in medium containing only EGF and Rspondin (ER medium).
2013-10-23 | E-GEOD-44060 | biostudies-arrayexpress
Project description:Chief cells expressing Wnt/R-spondin target genes are located in the stomach corpus gland base. These cells can act as reserve stem cells and their transdifferentiation is a hallmark of spasmolytic polypeptide expressing metaplasia (SPEM). Mechanisms that control their differentiation, transdifferentiation and re-differenitiation are not fully understood. We investigated the function of R-spondin 3, a Wnt signaling activator and Lgr5 ligand, by using conditional mouse models that enable manipulation of R-spondin 3 gene expression in gastric myofibroblasts.The effect and the physiological function of R-spondin 3 was analyzed in the corpus and colon with R-spondin 3 gene knock-out mice in Myh11+ myofibroblasts (Myh11-CreERT2; Rspo3fl/fl (RSPO3 KO) or R-spondin 3 gene knock-in overexpressiong myofibroblasts ( Myh11-CreERT2/Rosa26Sor6(CAG–Rspo3) ( RSPO3 KI)).
2022-01-01 | GSE145087 | GEO
Project description:We isolated quiescent CSCs using chemoradiotherapy resistance assays on tumors of MMTV-PyMT transgenic (specific breast cancer model) mice. We found that quiescent CSCs specifically expressed SETD4 without exception, and beyond activation exhibited high capacity of tumor-initiation in vivo and tumorsphere formation in vitro. Quiescent CSCs expressed high levels of ALDH1 and CD44 and low levels of CD24, that corresponds with their use as breast CSCs markers. Quiescent CSCs were showed to be resistant and able to survive under chemoradiotherapy treatment in either in vivo or in vitro models. Similarly, SETD4 overexpression caused cells extracted from tumors to exhibit clear chemoradiotherapy resistance. Transcriptomic analysis revealed that the molecular processes associated with cellular quiescence included those of DNA damage response and the Wnt/β-catenin signaling pathway. Together with our previous results, these findings showed that SETD4 marks quiescent CSCs and suggest that SETD4-marked quiescent CSCs could be used as key targets in clinical treatment for multiple cancers.
2021-01-24 | GSE165380 | GEO
Project description:Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman’s age is correlated to lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activation (EGA) relies on maternal RNA and proteins. Age and ovarian reserve both affects oocyte developmental competence, however, their relative importance in this process are difficult to tease out, as ageing is accompanied by a decrease in ovarian reserve. Oocytes store large quantities of RNA, including several noncoding transcripts (ncRNAs) involved in early development transcription and translation modulation. Despite the central role of ncRNAs in maternal to zygote transition, no characterization of the ncRNA transcriptome in human oocytes has been reported. This study aims at identifying how the human oocyte transcriptome changes across reproductive ages and ovarian reserve levels, with the goal of identifying candidate markers of developmental competence, and to assess the independent relevance of age and ovarian reserve in the changes of the transcriptome
2017-08-29 | GSE87201 | GEO
Project description:Mac-1 marks a quiescent and functionally superior HSC subset during regeneration
| PRJNA927024 | ENA