Details

Autor(en) / Beteiligte

• Holloway, Emily M.
• Wu, Joshua H.
• Czerwinski, Michael
• Sweet, Caden W.
• Wu, Angeline
• Tsai, Yu-Hwai
• Huang, Sha
• Stoddard, Amy E.
• Capeling, Meghan M.
• Glass, Ian
• Spence, Jason R.

Titel

Differentiation of Human Intestinal Organoids with Endogenous Vascular Endothelial Cells

Ist Teil von

• Developmental cell, 2020-08, Vol.54 (4), p.516-528.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) lack some cellular populations found in the native organ, including vasculature. Using single-cell RNA sequencing (scRNA-seq), we have identified a population of endothelial cells (ECs) present early in HIO differentiation that declines over time in culture. Here, we developed a method to expand and maintain this endogenous population of ECs within HIOs (vHIOs). Given that ECs possess organ-specific gene expression, morphology, and function, we used bulk RNA-seq and scRNA-seq to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC gene signatures. By comparing these gene signatures and validated markers to HIO ECs, we find that HIO ECs grown in vitro share the highest similarity with native intestinal ECs relative to kidney and lung. Together, these data demonstrate that HIOs can co-differentiate a native EC population that is properly patterned with an intestine-specific EC transcriptional signature in vitro. [Display omitted] •scRNA-seq reveals ECs in early hPSC-derived intestinal organoids•VEGF, BMP4, and FGF2 used to expand and maintain endogenous ECs•RNA-seq identifies organ-enriched human intestine, lung, and kidney EC profiles•Intestinal organoid ECs most closely resemble native intestinal ECs Holloway et al. investigate cellular heterogeneity during hPSC-derived intestinal organoid development and identify resident endothelial cells (ECs). ECs are usually lost over time but can be expanded using modified media conditions. In vivo human organ-specific EC signatures reveal that organoid ECs have the highest transcriptional similarity to native intestinal ECs.