Splicing variant of TGF-beta2 and uses thereof
OwnerHans-Willem Snoeck, Juhyun Choiinventors
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Abstract
An alternatively spliced form of transforming growth factor-beta2 (TGF-β2), herein denoted Δ6-TGF-β2 is disclosed. Δ6-TGF-β2 differs from TGF-β2 in the sequence of the three C-terminal exons. This novel protein is secreted, induced by cytotoxic stress in hematopoietic stem cells, and specifically blocks the enhancing effects of TGF-β2 on adult stem cells. Δ6-TGF-β2 can be used to protect stem cells from cytotoxic stress, and to enhance maintenance of these cells in vitro during retroviral transduction. In addition, Δ6-TGF-β2 can be used to slow aging and extend longevity.
Claims21
A method of protecting stem cells from stress comprising contacting the stem cells with a functional portion of Δ6-TGF-β2.
A method of enhancing the transduction of stem cells with a recombinant vector comprising contacting the stem cells undergoing transduction with a functional portion of Δ6-TGF-β2.
A method of inducing quiescence in stem cells comprising contacting stem cells with a functional portion of Δ6-TGF-β2.
A method for maintaining and expanding hematopoietic stem cells during culture in vitro, comprising
- contacting the stem cells with a functional portion of Δ6-TGF-β2;
- and
- culturing the hematopoietic stem cells in the presence of a cell producing Δ6-TGF-β2 or a functional portion thereof.
A method for producing recombinant Δ6-TGF-β2, comprising,
- expressing a functional portion of Δ6-TGF-β2 in a cell containing a vector operably configured to express the functional portion of Δ6-TGF-β2 from a nucleic acid sequence encoding the functional portion of Δ6-TGF-β2 and
- obtaining the functional portion of Δ6-TGF-β2 from at least one of the cell line and a media into which the cell line secretes the Δ6-TGF-β2.
An isolated nucleic acid sequence comprising a sequence that encodes a functional portion of Δ6-TGF-β2.
A composition comprising an isolated functional portion of Δ6-TGF-β2.
Dependencies are inferred from the claim text.