Human brown adipose derived stem cells and uses
An isolated human brown adipose tissue stem cell line. In one embodiment, the isolated human brown adipose tissue stem cell line expresses the markers CD9, SSEA4, CD44, CD90, CD166, CD73, but not CD14, CD34, CD45 or STRO-1. In another embodiment, the isolated human brown adipose tissue stem cell line expresses the genes UCP1, PPARGC1A, NRF1, FOXC2, CREB1, SIRT3, and WNT5A (REFX). In still another embodiment, the isolated human brown adipose tissue stem cell line is capable of differentiating into osteoblasts, chondrocytes, and adipocytes.
1. A human neonatal brown adipose tissue differentiated cell derived from an isolated human neonatal brown adipose tissue stem cell,
wherein the isolated human neonatal brown adipose tissue stem cell is grown in a culture medium comprising fibronectin type III domain-containing protein 5 (FNDC5) and differentiates into the human neonatal brown adipose differentiated cell;
wherein UCP-1, ELOVL3, and PGC1A gene expression is upregulated in the human neonatal brown adipose tissue differentiated cell.
2. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell is derived from a one day old male neonate.
3. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the human neonatal brown adipose tissue differentiated cell is a human brown adipocyte.
4. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell further expresses at least one of CREB1, DIO2, IRS1, MAPK14, NRF1, FOXC2, PPARD, PGC1-B, PRDM16, SRC, and WNT5A.
5. The human neonatal brown adipose tissue differentiated cell of claim 4 , wherein the isolated human neonatal brown adipose tissue stem cell is derived from a one day old male neonate.
6. The human neonatal brown adipose tissue differentiated cell of claim 4 , wherein the human neonatal brown adipose tissue differentiated cell is a human brown adipocyte.
7. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell further expresses at least one of PPARGC1A and SIRT3.
8. The human neonatal brown adipose tissue differentiated cell of claim 7 , wherein the isolated human neonatal brown adipose tissue stem cell is derived from a one day old male neonate.
9. The human neonatal brown adipose tissue differentiated cell of claim 7 , wherein the human neonatal brown adipose tissue differentiated cell is a human brown adipocyte.
10. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell is positive for the following cell surface markers: CD9, SSEA4, CD44, CD90, CD166, and CD73, and is negative for the following cell surface markers: CD14, CD34, CD45, and STRO-1.
11. The human neonatal brown adipose tissue differentiated cell of claim 10 , wherein the isolated human neonatal brown adipose tissue stem cell is derived from a one day old male neonate.
12. The human neonatal brown adipose tissue differentiated cell of claim 10 , wherein the human neonatal brown adipose tissue differentiated cell is a human brown adipocyte.
13. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell further expresses at least one of GATA, KLF2, and KLF3.
14. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell is grown in a culture medium comprising fibronectin type III domain-containing protein 5 (FNDC5) and 10% platelet lysate.
15. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein the isolated human neonatal brown adipose tissue stem cell does not express STRO-1.
16. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein UCP-1 gene expression is upregulated in the human neonatal brown adipose tissue differentiated cell.
17. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein ELOVL3 gene expression is upregulated in the human neonatal brown adipose tissue differentiated cell.
18. The human neonatal brown adipose tissue differentiated cell of claim 1 , wherein PGC1A gene expression is upregulated in the human neonatal brown adipose tissue differentiated cell.