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Helminth-induced reprogramming of the stem cell niche inhibits type 2 immunity [Bulk RNA-seq]

ABSTRACT: Helminth-induced reprogramming of the stem cell niche inhibits type 2 immunity [Bulk RNA-seq]

PROVIDER: PRJNA818973 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18441627_1.fastq.gz	Fastqsanger.gz
	SRR18441627_2.fastq.gz	Fastqsanger.gz
	SRR18441628_1.fastq.gz	Fastqsanger.gz
	SRR18441628_2.fastq.gz	Fastqsanger.gz
	SRR18441629_1.fastq.gz	Fastqsanger.gz

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Helminth-induced reprogramming of the stem cell niche inhibits type 2 immunity

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Helminth-induced reprogramming of the stem cell niche inhibits type 2 immunity [Bulk RNA-seq]

Project description:Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the symbiotic parasite Heligmosomoides polygyrus bakeri (Hpb), reprograms the intestinal epithelium into a fetal-like state marked by the emergence of Clusterin-expressing revival stem cells (revSCs). Organoid-based studies using parasite-derived excretory/secretory products reveal that Hpb-mediated revSC generation occurs independent of host-derived immune signals and inhibits type 2 cytokine-driven differentiation of secretory epithelial lineages that promote their expulsion. Reciprocally, type 2 cytokine signals limit revSC differentiation and, consequently, Hpb fitness indicating that helminths compete with their host for control of the intestinal stem cell niche to promote continuation of their life cycle.

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Helminth-induced reprogramming of the stem cell niche inhibits type 2 immunity

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

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Self-Assembling Hematopoietic Niche on a Chip: Bulk sequencing to investigate effect of proton radioablation

Project description:(Radiation Experiments: bulk sequencing data) Here we present an integrative, bottom-up approach towards emulating the human bone marrow in vitro. Our method harnesses the regenerative capacity of adult stem cells to self-assemble a complex, specialized microenvironment of human hematopoietic stem cells (HSCs) in a vascularized three-dimensional microphysiological system. Through flow cytometry and single-cell transcriptomic interrogation, we show that the microengineered niche can reconstitute HSC self-renewal, multilineage hematopoiesis, and complex ligand-receptor signaling pathways of the native human marrow. The ability of our model to generate functionally mature myeloid cells also makes it possible to mimic the key physiological processes of innate immunity including neutrophil chemotaxis and intravascular mobilization. To demonstrate the advanced application of the bone marrow-on-a-chip, we present i) a specialized model of bone marrow ablation by proton beam radiotherapy and ii) a multiorgan model of innate immune response against bacterial lung infection. This work advances our ability to reconstruct, probe, and deconvolve the complexity of the bone marrow niche, and may enable new capabilities to model human hematopoiesis and immunity for biomedical and pharmaceutical applications.

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