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Single cell-guided prenatal derivation of primary fetal epithelial organoids from the human amniotic and tracheal fluids

ABSTRACT: Single cell-guided prenatal derivation of primary fetal epithelial organoids from the human amniotic and tracheal fluids

PROVIDER: PRJNA912221 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR22741600.fastq.gz	Fastqsanger.gz
	SRR22741700.fastq.gz	Fastqsanger.gz
	SRR22741601.fastq.gz	Fastqsanger.gz
	SRR22741701.fastq.gz	Fastqsanger.gz

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Single cell-guided prenatal derivation of primary fetal epithelial organoids from the human amniotic and tracheal fluids

Project description:Isolation of tissue-specific fetal stem cells and derivation of primary organoids is currently limited to post-termination samples. This hampers the prenatal investigation of fetal development and congenital diseases. Therefore, novel patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue or cellular reprogramming, would be advantageous. The amniotic fluid (AF) is a source of cells originating from multiple developing organs. Using single cell analysis, we characterised the cellular identities present in the human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids (AFO) exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modelling, we derived lung organoids from the amniotic and tracheal fluid cells of Congenital Diaphragmatic Hernia (CDH) fetuses. CDH organoids show differences to non-CDH controls recapitulating some features of the disease. AFO are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalised to the fetus at clinically relevant developmental stages.

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Project description:Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.

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Author Correction: Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.

Project description: Not available

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