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Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [scRNA-seq]

ABSTRACT: Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [scRNA-seq]

PROVIDER: PRJNA904756 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22396971.fastq.gz	Fastqsanger.gz
	SRR22396972.fastq.gz	Fastqsanger.gz

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Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis

Project description:Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis

| PRJNA904761 | ENA

Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [scRNA-seq]

Project description:Stem cell dynamics in the lung govern homeostasis, repair, and regeneration, yet there is still much unknown about the mechanisms of these processes. Furthermore, incongruencies between murine and human physiology limit the translation of some findings. In this work, we address these limitations by using a transgenic pig model to identify two populations of LGR5+ cells in the lung that are present in the human but that are absent from the mouse. Using RNA sequencing, 3D imaging, organoid models, and differentiation assays, we determine that in the fetal lung, epithelial LGR5 expression is transient in a subpopulation of developing lung bud tips. While epithelial LGR5 expression is absent from postnatal lung, it is reactivated in some organoids derived from basal airway cells. A separate population of LGR5+ cells is mesenchymal, surrounds developing and mature airways, is closely associated with nerve fibers, and acts as a multipotent progenitor cell capable of supporting the airway basal cell niche. These results point to two roles for LGR5 in orchestrating stem and progenitor cell dynamics, and provide a physiologically relevant model for further studies on the role of these populations in repair and regeneration.

2023-11-15 | GSE218650 | GEO

Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [Bulk RNA-seq]

2023-11-15 | GSE218657 | GEO

Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [Bulk RNA-seq]

Project description:Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis [Bulk RNA-seq]

| PRJNA904768 | ENA

Transgenic porcine model reveals two roles for LGR5 during lung development and homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-15 | GSE218658 | GEO

A constant pool of Lgr5+ intestinal stem cells is required for intestinal homeostasis

Project description:Lgr5+ crypt base columnar cells, the operational intestinal stem cells (ISCs), are thought to be dispensable for small intestinal (SI) homeostasis. Using a novel Lgr5-2A-DTR (Diphtheria Toxin Receptor) model which ablates Lgr5+ cells with near-complete efficiency and retains endogenous levels of Lgr5 expression, we show that persistent depletion of Lgr5+ ISCs in fact compromises SI epithelial integrity and reduces epithelial turnover in vivo. In vitro, Lgr5-2A-DTR SI organoids are unable to establish or survive when Lgr5+ ISCs are continuously eliminated when DT is in the media. However, transient exposure to DT at the start of culture allows organoids to form, and the rate of outgrowth reduces with increasing length of DT presence. Our results indicate that intestinal homeostasis requires a constant pool of Lgr5+ ISCs, which is supplied by rapidly reprogrammed non-Lgr5+ crypt populations when pre-existing Lgr5+ ISCs are ablated.

2020-12-31 | GSE148727 | GEO

Gene expression profiles of DLD1 cells in which GATA6 or LGR5 expression was suppressed.

Project description:Mutations in APC or β-catenin that cause aberrant activation of Wnt signaling are responsible for the initiation of colorectal tumor development. LGR5 is specifically expressed in stem cells of the intestine, stomach and hair follicle, and plays essential roles in maintaining tissue homeostasis. LGR5-positive stem cells have been shown to be responsible for the intestinal adenoma initiated by some mutations in APC . Furthermore, it has recently been reported that Lgr5, which is associated with the Frizzled/Lrp Wnt receptor complex, interacts with R-spondins and thereby activates Wnt signaling. However, the function of LGR5 in colorectal tumorigenesis has been unclear. Here we show that LGR5 is required for the tumorigenicity of colorectal cancer cells. We also show that the transcription factor GATA6 directly enhances the expression of LGR5. DLD1 cells were infected with a lentivirus expressing an shRNA targeting GATA6 or LGR5.

2011-10-17 | E-GEOD-32987 | biostudies-arrayexpress

RNA-seq of mouse Lgr5+ intestinal stem cells and progenitors following Lkb1 deletion against controls

Project description:Perturbed intestinal epithelial homeostasis demonstrated as decreased Lgr5+ intestinal stem cells (Lgr5 ISCs) and increased secretory lineages were observed in our study where Lkb1 was specfically deleted in Lgr5 ISCs using Lgr5-EGFP-creERT2 (Tamoxifen) deletor. To gain mechanistic insight how Lkb1 maintains intestinal epithelial stem cell homeostasis, Lkb1 deficient ISCs (Lgr5-high cells) and progenitors (Lgr5-low cells) are isolated by flow cytometry and profiled by RNA sequencing to compare with controls (Lkb1 wild type ISCs and progenitors).

2020-02-29 | E-MTAB-6501 | biostudies-arrayexpress

LGR5 is a conserved marker of hair follicle stem cells across species

Project description:Using a transgenic pig expressing H2B-GFP under the control of the endogenous LGR5 promoter, we used fluorescence activated cell sorting to isolate LGR5-high and LGR5-negative epidermal cells to generate mRNA profiles of the hair follicle stem cell population, n=2 pigs. Bulk RNAseq samples were prepared from porcine cells, at least 500ng of RNA was extracted from sorted LGR5-GFP-high or LGR5-GFP-negative populations. RNAseq was performed externally by GENEWIZ; library preparation with poly(A) selection was performed followed by paired end 150bp sequencing on Illumina HiSeq.

2021-12-04 | GSE190069 | GEO

Ablating Lgr5-expressing prostatic stromal cells activates the ERK-mediated mechanosensory signaling and disrupts prostate tissue homeostasis

Project description:The heterogeneity of the prostate stromal cells is widely appreciated but the functional implication remains incompletely understood. Using genetic lineage tracing and light-sheet imaging, we show that some fibroblast cells near the junction of the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5+ stromal cells. These changes are not mediated via endocrine or nervous regulation but can be phenocopied by physical disruption of prostatic lumen integrity. RNA-Seq analysis implies that ablating the Lgr5+ stromal cells activates a mechanosensory response, which is supported by increased prostate tissue stiffness and activation of the mitogen-activated protein kinase (MAPK). Suppressing MAPK overrides the increased epithelial proliferation. This study demonstrates that the Lgr5+ stromal cells regulate tissue homeostasis in a long-distance manner by maintaining anatomic integrity and implies that the cells near the transitional regions between organs likely control organ homeostasis by sustaining a balanced mechanoforce.

2023-01-06 | GSE190938 | GEO

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