Journal
DEVELOPMENTAL CELL
Volume 54, Issue 4, Pages 516-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2020.07.023
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Funding
- Intestinal Stem Cell Consortium [U01DK103141]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Heart Lung and Blood Institute (NHLBI) [R01HL119215]
- NIAID Novel Alternative Model Systems for Enteric Diseases (NAMSED) [U19AI116482]
- Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation [CZF2019-002440]
- NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [5R24HD000836]
- Training in Basic and Translational Digestive Sciences Training Grant (NIH-NIDDK) [5T32DK094775]
- Cellular Biotechnology Training Program training grant (NIH-NIGMS) [2T32GM008353]
- Ruth L. Kirschstein Predoctoral Individual National Research Service Award (NIH-NHLBI) [F31HL146162]
- Training Program in Organogenesis (NIH-NICHD) [T32 HD007505]
- NSF-GRFP [DGE 1256260]
- University of Michigan Center for Gastrointestinal Research (UMCGR) (NIDDK) [5P30DK034933]
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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.
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