Dataset Information

Characterization of mesenchymal support required for in vivo engraftment and development of human PSC-derived organoids

ABSTRACT: Human gastrointestinal (GI) organoids derived from pluripotent stem cells have unique potential for studying organogenesis, physiology, and diseases. To this end, their transplantation into animal models to further their development into functional organs provides a valuable tool. However, organoids from different GI regions, for example, the esophagus or intestine, harbor different engraftment capabilities. Here, we developed a tissue-engineering approach and show that enhancing the mesenchyme-to-endoderm ratio enables reliable engraftment of GI organoids. However, endoderm/mesoderm recombinations reveal that only Human Intestinal Organoid (HIO) mesenchyme allows full development of GI epitheliums in vivo. Comparative mesenchyme analysis from esophageal, gastric, intestinal, and colonic organoids shows endothelial cell enrichment within the HIO mesenchyme, and we demonstrate by endothelial cell depletion or addition that these cells are required and sufficient for proper GI organoid development in vivo. Our findings highlight the optimal mesenchymal cellular composition needed to support GI organoid engraftment, tissue growth, and function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262403 | GEO | 2025/01/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Underdeveloped lungs are the primary cause of death in premature infants, however, little is known about stem and progenitor cell maintenance during human lung development. In this study, we have identified that FGF7, Retinoic Acid and CHIR-99021, a small molecule that inhibits GSK3 to activate Wnt signaling, support in vitro maintenance of primary human fetal lung bud tip progenitor cells in a progenitor state. Furthermore, these factors are sufficient to derive a population of human bud tip-like progenitor cells in 3D organoid structures from human pluripotent stem cells (hPSC). Functional studies showed that hPSC-derived bud tip progenitor organoids do not contain any mesenchymal cell types, maintain multilineage potential in vitro and are able to engraft into the airways of injured mice and respond to systemic factors. We performed RNA-sequencing to assess the degree of similarity in global gene expression profiles between the full human fetal lung (59-127 days gestation), isolated human fetal bud tip progenitors, organoids grown from primary fetal bud tip progenitors, and hPSC-derived bud tip organoids. Results showed that hPSC-derived organoids have molecular profiles similar to organoids generated from primary human fetal lung tissue. Gene expression differences between hPSC-derived bud tip organoids and fetal progenitor organoids may be related to the presence of contaminating mesenchymal cells in primary cultures. hPSC-derived bud tip organoids are generated from a well-defined human cell sources, offering a distinct advantage over rare primary tissue as a means to study human specific lung development, homeostasis and disease. Sample Nomenclature - Description ------------------------------------------------------------------------- Peripheral fetal lung the distal/peripheral portion of the fetal lung (i.e., distal 0.5 cm) was excised from the rest of the lung using a scalpel. This includes all components of the lung (e.g., epithelial, mesenchymal, vascular). Isolated fetal bud tip the bud peripheral portion of the fetal lung was excised with a scalpel and subjected to enzymatic digestion and microdissection. The epithelium was dissected and separated from the mesenchyme, but a small amount of associated mesenchyme likely remained. Fetal progenitor organoid 3D organoid structures that arose from culturing isolated fetal epithelial bud tips. Foregut spheroid 3D foregut endoderm structure as described in Dye et al. (2015). Gives rise to patterned lung organoid (PLO) when grown in 3F medium. Patterned lung organoid (PLO) lung organoids that were generated by differentiating hPSCs, as described throughout the manuscript. Bud tip organoid organoids derived from PLOs, enriched for SOX2/SOX9 co-expressing cells, and grown/passaged in 3F medium.

Dataset Information

Characterization of mesenchymal support required for in vivo engraftment and development of human PSC-derived organoids

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets