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A lymphatic-stem cell interactome regulates intestinal stem cell activity

ABSTRACT: A lymphatic-stem cell interactome regulates intestinal stem cell activity

PROVIDER: PRJNA785618 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17099989.fastq.gz	Fastqsanger.gz
	SRR17099990.fastq.gz	Fastqsanger.gz
	SRR17099991.fastq.gz	Fastqsanger.gz
	SRR17099992.fastq.gz	Fastqsanger.gz
	SRR17099993.fastq.gz	Fastqsanger.gz

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A lymphatic-stem cell interactome regulates intestinal stem cell activity

Project description:Single-cell RNA-sequencing of murine small intestinal organoid cultured with and without lymphatic endothelial cells: Purpose: To identify differences in cell composition in murine organoids upon coculture with lymphatic endothelial cells Results: We recovered 818 cells with a median of 37750 UMIs per cell for the organoid alone and 1233 cells with a median of 79354 UMIs per cells for the cocultured organoid condition. Conclusions: scRNASeq reveals different cell composition in organoids cocultured with lymphatic endothelial cells compared to control Single-cell RNA-Sequencing of murine small and large intestinal tissue: Purpose: To generate a reference dataset of all major cell types present in the small and large intestine of the mouse Results: For the small intestine we recovered 8842 cells with a median of 4088 UMIs per cell compared to 8646 cells with a median of 10009 UMIs per cell for the large intestine. Conclusions: scRNASeq recovers all of the major epithelial, immune and stromal cell types in the intestine. Spatial transcriptomic profiling of murine small and large intestine: Purpose: To spatially map the major cell types in the mouse intestine and infer cell:cell communication from neighboring cells Conclusions: Spatial transcriptomic profiling of the mouse small and large intestine reveals all major cell types and allows for cell:cell signaling analyses upon integration with our matching scRNA-Seq data

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Project description:In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigated the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discovered that lymphatic drainage insufficiency (LDI) started on day one and persisted for up to two weeks following the fracture. Sufficient lymphatic drainage facilitates fracture healing. Furthermore, we identified that lymphatic platelet thrombosis (LPT) blocked the draining lymphoid sinus and LVs, caused LDI, and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage decreased neutrophils and increased M2-like macrophages of the hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). Lymphatic platelet thrombolysis also benefits senile fracture healing. These findings demonstrate that LPT limits bone regeneration by impeding lymphatic transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone repair.

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Project description:Lymphatic vessels (LVs) interdigitated with blood vessels, travel and form an extensive transport network in the musculoskeletal system. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, by near infrared indocyanine green lymphatic imaging (NIR-ICG), we examined lymphatic drainage function at the tibial fracture sites and found lymphatic drainage insufficiency (LDI) occurred as early as two weeks after fracture. Sufficient lymphatic drainage facilitates fracture healing. In addition, we identified that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, caused LDI and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage inhibits neutrophils influx and induce M2-like macrophages palarization of hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). These findings demonstrate that LPT limits fracture healing by blocking lymphatic drainage from transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone fracture healing.

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