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Generation of Functional Endodermal Hepatic Organoids
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Endoderm generates endothelial cells during liver development.

Orit Goldman1, Songyan Han1, Wissam Hamou1

  • 1Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.

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This summary is machine-generated.

Endothelial cells (ECs), crucial for organ development, can originate from both mesoderm and endoderm. This study reveals endoderm-derived progenitor cells generate functional ECs during liver development.

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Organogenesis relies on the vascular plexus formation via angiogenesis.
  • Endothelial cells (ECs) are traditionally considered mesodermal derivatives.
  • The origin of ECs in endoderm-derived organs remains incompletely understood.

Purpose of the Study:

  • To investigate the origin of endothelial cells (ECs) during liver development.
  • To determine if endoderm-derived cells can contribute to the vascular network in developing organs.

Main Methods:

  • Utilized human and mouse embryonic stem cell models for hepatic differentiation.
  • Employed KDR (VEGFR2/FLK-1) and FOXA2 markers to identify progenitor cells.
  • Performed lineage tracing in Foxa2 lineage-tracing mouse embryos.

Main Results:

  • Identified a subset of FOXA2+ endoderm-derived progenitor cells expressing KDR that generate functional ECs.
  • Demonstrated that KDR+FOXA2+ endoderm cells in hepatic cultures produce ECs.
  • Confirmed FOXA2+ cell-derived CD31+ ECs integrate into the fetal liver vascular network in vivo.

Conclusions:

  • Endothelial cells (ECs) can originate from endoderm, not exclusively mesoderm.
  • Endoderm-derived progenitor cells contribute to vascularization in endoderm-derived organs like the liver.
  • This finding expands the understanding of cell lineage and vascular development.