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AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Distal Stomach

ABSTRACT: AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Distal Stomach

PROVIDER: PRJNA549866 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9331360_1.fastq.gz	Fastqsanger.gz
	SRR9331360_2.fastq.gz	Fastqsanger.gz
	SRR9331370_1.fastq.gz	Fastqsanger.gz
	SRR9331370_2.fastq.gz	Fastqsanger.gz
	SRR9331361_1.fastq.gz	Fastqsanger.gz

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AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Distal Stomach

Project description:Isolating adult stem cells from human stomach epithelia has proven challenging due to a lack of surface markers that are amenable to antibody-based sorting approaches. Here, through comparative expression profiling of mouse Lgr5+ adult stem cells along the gastrointestinal tract, we identify novel pylorus-specific stem cell markers, including the membrane protein Aqp5. FACS-based isolation of endogenous AQP5+ cells from healthy human pyloric stomach revealed their stem cell identity in organoid assays. Using new Aqp5-driven CreERT2 mouse models to selectively target conditional mutations to the pyloric stem cell compartment in vivo, we establish pyloric stem cells as a major source of Wnt-driven invasive gastric cancer. The new stem cell markers and mouse models described here will be an invaluable resource for deciphering early gastric cancer formation and for isolating and characterizing human stomach stem cells as a prerequisite to potentially exploiting their regenerative medicine potential in the clinic.

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AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Mouse and Human Pyloric Stomach

Project description:AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Mouse and Human Pyloric Stomach

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AQP5-Expressing Cells Serve as Stem Cells and Cancer Origins in the Mouse and Human Pyloric Stomach

Project description:Isolating adult stem cells from human stomach epithelia has proven challenging due to a lack of surface markers that are amenable to antibody-based sorting approaches. Here, through comparative expression profiling of mouse Lgr5+ adult stem cells along the GI tract, we identify novel pylorus-specific stem cell markers, including the membrane protein Aqp5. FACS-based isolation of endogenous AQP5+ cells from healthy human pyloric stomach revealed their stem cell identity in organoid assays. Using new Aqp5-driven CreERT2 mouse models to selectively target conditional mutations to the pyloric stem cell compartment in vivo, we establish pyloric stem cells as a major source of Wnt-driven invasive gastric cancer. The new stem cell markers and mouse models described here will be an invaluable resource for deciphering early gastric cancer formation and for isolating and characterizing human stomach stem cells as a prerequisite to potentially exploiting their regenerative medicine potential in the clinic.

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Accelerated growth in the absence of DNA replication origins

Project description:DNA replication initiates at defined sites called origins, which serve as binding sites for initiator proteins that recruit the replicative machinery. Origins differ in number and structure across the three domains of life1 and their properties determine the dynamics of chromosome replication. Bacteria and some archaea replicate from single origins, whilst most archaea and all eukaryotes replicate using multiple origins. Initiation mechanisms that rely on homologous recombination operate in some viruses. Here we show that such mechanisms also operate in archaea. We have used deep sequencing to study replication in Haloferax volcanii. Four chromosomal origins of differing activity were identified. Deletion of individual origins resulted in perturbed replication dynamics and reduced growth. However, a strain lacking all origins has no apparent defects and grows significantly faster than wild-type. Origin-less cells initiate replication at dispersed sites rather than at discrete origins and have an absolute requirement for the recombinase RadA, unlike strains lacking individual origins. Our results demonstrate that homologous recombination alone can efficiently initiate the replication of an entire cellular genome. This raises the question of what purpose replication origins serve and why they have evolved. Measurement of replication dynamics (marker frequency analysis; MFA) for Haloferax volcanii strains, including wild-type, the laboratory strain, individual and combinations of replication origin deletions.

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