Generation of induced human thymic epithelial cells and its application in cell-based immunotherapies
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsKatja G. WEINACHT, Hui Gai
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Abstract
Methods of differentiating pluripotent stem cells into thymic epithelial progenitor cells are provided.
Claims23
A method of differentiating a Definitive Endoderm (DE) cell or Anterior Foregut (AFG) cell or an Anterior Foregut (AFG) plus cell to a HOXA3+, TBX1+/high, bipotent PPEIII cell that has a committed fate to PPEIII and has the potency to further differentiate into thymus and parathyroid epithelial lineages, the method comprising culturing the DE cell or AFG cell or AFG plus cell in a medium comprising at least:
- a Transforming Growth Factor (TGF-β) signaling pathway inhibitor;
- a Bone Morphogenic Protein (BMP) signaling pathway inhibitor;
- a Retinoic Acid (RA) signaling pathway activator;
- a PI3K/AKT signaling pathway inhibitor,
- wherein the culturing of the DE or AFG or AFG-plus cell promotes differentiation to a bipotent PPEIII cell specified for PPEIII and primed for thymus or parathyroid fate.
6-8. (canceled)
A method of differentiating a HOXA3+, TBX1+/high, bipotent PPEIII cell to a human a TBX1dim, PAX1+, PAX9+, FOXG1+ ventral PPEIII cell that can further differentiate into thymic epithelial progenitor cells, the method comprising culturing the bipotent PPEIII cell in a medium comprising at least:
- a WNT signaling pathway activator;
- a BMP signaling pathway activator,
- wherein the culturing promotes differentiation of the bipotent PPEIII cell to a ventral PPEIII cell.
23-24. (canceled)
A method of differentiating a TBX1dim, PAX1+, PAX9+, FOXG1+ ventral PPEIII cell to a FOXN1+, PSMB11+, EPCAM+ TEPC cell, the method comprising culturing the ventral PPEIII cell in a medium comprising at least:
- an IFN type I or II signaling pathway activator;
- a FGF signaling pathway activator;
- and
- an IGF signaling pathway activator.
26-38. (canceled)
Dependencies are inferred from the claim text.