Methods and compositions for the production of oligodendrocyte progenitor cells
AssigneePresident and Fellows of Harvard College
InventorsParastoo Khoshakhlagh, Hon Man Alex Ng, George M. Church
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Abstract
Provided herein are pluripotent stem cells comprising particular combinations of transcription factor for the production of oligodendrocyte progenitor cells (OPCs). Also provided herein are methods of producing the pluripotent stem cells and methods of using the pluripotent stem cells to produce (OPCs) and oligodendrocytes.
Claims68
A pluripotent stem cell comprising at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1), (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4).
A method comprising:
- introducing into pluripotent stem cells at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1) (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4), optionally wherein each transcription factor is introduced on an engineered nucleic acid comprising a nucleotide sequence encoding the transcription factor, and optionally wherein at least two transcription factors are encoded by the same engineered nucleic acid;
- and
- culturing the pluripotent stem cells to produce a population of cells comprising oligodendrocyte progenitor cells (OPCs).
A method comprising:
- introducing into pluripotent stem cells at least one engineered nucleic acid encoding IL-10, IFNβ, or a combination thereof;
- introducing into the pluripotent stem cells at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1) (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4), optionally wherein each transcription factor is introduced on an engineered nucleic acid comprising a nucleotide sequence encoding the transcription factor, and optionally wherein at least two transcription factors are encoded by the same engineered nucleic acid;
- and
- optionally culturing the pluripotent stem cells to produce a population of cells comprising oligodendrocyte progenitor cells (OPCs).
A pluripotent stem cell or an oligodendrocyte progenitor cell comprising OCT4, OLIG2, NKX6.1, and SOX9.
A pluripotent stem cell or an oligodendrocyte progenitor cell comprising OCT4, OLIG2, and SOX9.
A pluripotent stem cell or an oligodendrocyte progenitor cell comprising OLIG2, NKX6.1, and SOX9.
A pluripotent stem cell engineered to express IL-10 and/or IFNβ, optionally wherein the pluripotent stem cell is an induced pluripotent stem cell.
An oligodendrocyte progenitor cell engineered to express IL-10 and/or IFNβ.
A method comprising:
- introducing into pluripotent stem cells at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1) (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4), optionally wherein each transcription factor is introduced on an engineered nucleic acid comprising a nucleotide sequence encoding the transcription factor, and optionally wherein at least two transcription factors are encoded by the same engineered nucleic acid;
- culturing the pluripotent stem cells to produce a population of cells comprising oligodendrocyte progenitor cells (OPCs);
- and
- culturing the OPCs, optionally with another cell type, to produce a myelinated organoid.
A method comprising:
- introducing into pluripotent stem cells at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1) (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4), optionally wherein each transcription factor is introduced on an engineered nucleic acid comprising a nucleotide sequence encoding the transcription factor, and optionally wherein at least two transcription factors are encoded by the same engineered nucleic acid to produce engineered pluripotent stem cells capable of expressing at least four transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1) (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4).
A pluripotent stem cell comprising at least three transcription factors selected from (a) oligodendrocyte 2 (OLIG2), (b) SRY-box 9 (SOX9), (c) NKX homeobox 6.1 (NKX6.1), (d) NKX homeobox 6.2 (NKX6.2), and (e) octamer-binding 4 (OCT4).
The pluripotent stem cell of claim 67 comprising OCT4, SOX9, and OLIG2.
Dependencies are inferred from the claim text.