METHODS OF DIFFERENTIATING STEM CELLS INTO ONE OR MORE CELL LINEAGES
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Abstract
The present disclosure provides an understanding of the regulation of the developmental phases of stem cells and their induction into relevant cell lineages, such as primitive streak, endoderm, mesoderm, or subterrotories of endoderm'"'"'s. In particular, the present disclosure provides methods, culture medium and kits for the maintenance and differentiation of stem cells into relevant cell lineages.
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Citations
76 Claims
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1-56. -56. (canceled)
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57. A method of differentiating anterior primitive streak cells into definitive endoderm (DE) lineage, comprising contacting said anterior primitive streak cells with:
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a) one or more activators of TGFβ
/Nodal signaling; andb) one or more inhibitors of BMP signaling or one or more inhibitors of Wnt signaling, to produce cells of the definitive endoderm (DE) lineage. - View Dependent Claims (58, 61, 63, 73, 74, 75, 76)
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59. (canceled)
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60. A method of differentiating cells of the DE lineage into cells of the posterior foregut (PFG), by contacting said cells of the DE with retinoic acid, a BMP inhibitor, a Wnt inhibitor and a FGF/MAPK inhibitor.
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62. A method of differentiating cells of the DE lineage into cells of the midgut/hindgut (MHG), by contacting said DE cells with a BMP activator, a Wnt activator and FGF activator.
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64. A method of inducing pancreatic progenitors of the PFG from the DE within three days by contacting said PFG with:
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a) one or more FGF/MAPK inhibitors; b) one or more BMP inhibitors; and c) retinoic acid (RA).
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65. A method of inducing liver progenitors of the PFG from the DE within four days by contacting said PFG with:
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a) one or more TGFβ
inhibitors;b) retinoic acid (RA); c) one or more BMP activators, and d) one or more Wnt inhibitors.
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66. A cell culture medium for differentiating a stem cell into definitive endoderm comprising one or more of the following factors:
- one or more activators of TGFβ
/Nodal signaling, one or more activators of Wnt signaling;
one or more inhibitors of PI3K/mTOR signaling;
one or more activators of TGFβ
/Nodal signaling;
one or more inhibitors of BMP signaling or one or more inhibitors of Wnt signaling.
- one or more activators of TGFβ
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67. (canceled)
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68. A cell culture medium for differentiating cells of the DE lineage into cells of the posterior foregut (PFG) comprising one or more of the following factors:
- retinoic acid, a BMP inhibitor, a Wnt inhibitor or a FGF/MAPK inhibitor.
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69. A cell culture medium for differentiating cells of the DE lineage into cells of the midgut/hindgut (MHG), comprising one or more of the following factors:
- BMP activator, a Wnt activator or FGF activator.
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70. A cell culture medium for inducing pancreatic progenitors of the PFG from the DE comprising one or more of the following factors:
- a) one or more FGF/MAPK inhibitors;
b) one or more BMP inhibitors;
or c) retinoic acid (RA).
- a) one or more FGF/MAPK inhibitors;
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71. A cell culture medium for inducing liver progenitors of the PFG from the DE comprising one or more of the following factors:
- a) one or more TGF inhibitors;
b) one or more BMP activators, c) retinoic acid and d) one or more Wnt inhibitors.
- a) one or more TGF inhibitors;
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72. (canceled)
Specification