Jan 22, 2019

Generation of lung organoids from human pluripotent stem cells in vitro

Nature Protocols
Alyssa J MillerJason R Spence

Abstract

The lung epithelium is derived from the endodermal germ layer, which undergoes a complex series of endoderm-mesoderm-mediated signaling events to generate the final arborized network of conducting airways (bronchi, bronchioles) and gas-exchanging units (alveoli). These stages include endoderm induction, anterior-posterior and dorsal-ventral patterning, lung specification, lung budding, branching morphogenesis, and, finally, maturation. Here we describe a protocol that recapitulates several of these milestones in order to differentiate human pluripotent stem cells (hPSCs) into ventral-anterior foregut spheroids and further into two distinct types of organoids: human lung organoids and bud tip progenitor organoids. The resulting human lung organoids possess cell types and structures that resemble the bronchi/bronchioles of the developing human airway surrounded by lung mesenchyme and cells expressing alveolar-cell markers. The bud tip progenitor organoids possess a population of highly proliferative multipotent cells with in vitro multilineage differentiation potential and in vivo engraftment potential. Human lung organoids can be generated from hPSCs in 50-85 d, and bud tip progenitor organoids can be generated in 22 d. The two ...Continue Reading

  • References41
  • Citations19

References

  • References41
  • Citations19

Citations

Mentioned in this Paper

Biological Markers
Endoderm
In Vivo
MRNA Maturation
Regenerative Medicine
Pluripotent Stem Cells
Catheter Tip
Lung
Bronchioles
Cell Culture Techniques

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