Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter

Abstract

The present invention relates to a method of modulating production of neurons and/or oligodendrocytes from neural progenitor cells of human white matter and to a method of treating a subject for a condition modulated by underproduction of oligodendrocytes from human white matter. Both of these methods involve administering an agonist or antagonist of one or more molecules set forth in Tables 1 and/or 2 to the neural progenitor cells. Also disclosed is a method of using an inhibitor of sterol synthesis to differentiate oligodendrocyte progenitor cells to oligodendrocytes.

1 . A method of modulating production of neurons and/or oligodendrocytes from neural progenitor cells of human white matter, said method comprising: 
 administering an agonist or antagonist of one or more molecules set forth in Tables 1 and/or 2 to the neural progenitor cells under conditions effective to modulate production of neurons and/or oligodendrocytes.    
     
     
         2 . The method of  claim 1 , wherein the neural progenitor cells are oligodendrocyte progenitor cells.  
     
     
         3 . The method of  claim 1 , wherein the one or more molecules is set forth in Table 1.  
     
     
         4 . The method of  claim 1 , where in the one or more molecules is set forth in Table 2.  
     
     
         5 . The method of  claim 1 , wherein the one or more molecules is a receptor tyrosine phosphatase.  
     
     
         6 . The method of  claim 5 , wherein the one or more molecules is RPTP-zeta.  
     
     
         7 . The method of  claim 1 , wherein the one or more molecules is a chondrotin sulfate proteoglycan.  
     
     
         8 . The method of  claim 7 , wherein the one or more molecules is phosphocan, versican, neurocan, NG2, or neuroglycan C/NGC.  
     
     
         9 . The method of  claim 1 , wherein the one or more molecules is a syndecan.  
     
     
         10 . The method of  claim 9 , wherein the one or more molecules is syndecan-3.  
     
     
         11 . The method of  claim 1 , wherein the one or more molecules is adenylate cyclase 8.  
     
     
         12 . The method of  claim 1 , wherein the one or more molecules is selected from the group consisting of pleiotrophin, platelet-derived growth factor, NEL-like 1, neuralin 1, BMP2 (a Dpp homologue), OP-1, chromoganin B (secretogranin 1), or secretogranin II (chromogranin C).  
     
     
         13 . The method of  claim 12 , wherein one or more molecules is pleiotrophin.  
     
     
         14 . The method of  claim 12 , wherein the one or more molecules is NEL-like 1.  
     
     
         15 . The method of  claim 12 , wherein the one or more molecules is neuralin 1.  
     
     
         16 . The method of  claim 1 , wherein the one or molecules is a receptor tyrosine kinase.  
     
     
         17 . The method of  claim 1 , wherein the one or more molecules is platelet-derived growth factor receptor, cannabinoid receptor 1, G protein-coupled receptor 19, activated p21cdc42Hs kinase, or transmembrane 4 superfamily member 2.  
     
     
         18 . The method of  claim 1 , wherein the one or more molecules is GABA A receptor, glycine receptor beta, glutamate receptor ionotrophic AMPA 2, or glutamate receptor iontropic kainate 1.  
     
     
         19 . The method of  claim 1 , wherein one or more molecules is zinc finger DAZ interacting protein 1.  
     
     
         20 . The method of  claim 1 , wherein said administering is carried out in vivo.  
     
     
         21 . The method of  claim 1 , wherein said administering is carried out in vitro.  
     
     
         22 . The method of  claim 1 , wherein the neural progenitor cells are from a post-natal human.  
     
     
         23 . The method of  claim 1 , wherein the neural progenitor cells are from an adult human.  
     
     
         24 . The method of  claim 1 , wherein the neural progenitor cells are from a fetal human.  
     
     
         25 . The method of  claim 1 , wherein the one or more molecules modulate oligodendrocyte progenitor mobilization, division, proliferation, differentiation, and/or self-maintenance.  
     
     
         26 . The method of  claim 1 , wherein the one or more molecules modulate oligodendrocyte maturation, differentiation, myelin production, and/or axonal myelination.  
     
     
         27 . A method of treating a subject for a condition modulated by underproduction, dysfunction, or loss of oligodendrocytes from human white matter, said method comprising: 
 administering to the subject an agonist or antagonist of one or more molecules molecules set forth in Tables 1 and/or 2 under conditions effective to treat the condition modulated by underproduction, dysfunction, or loss of oligodendrocytes.    
     
     
         28 . The method of  claim 27 , wherein the one or more molecules is set forth in Table 1.  
     
     
         29 . The method of  claim 27 , wherein the one or more molecules is set forth in Table 2.  
     
     
         30 . The method of  claim 27 , wherein the one or more molecules is a receptor tyrosine phosphatase.  
     
     
         31 . The method of  claim 30 , wherein the one or more molecules is RPTP-zeta.  
     
     
         32 . The method of  claim 27 , wherein the one or more molecules is a chondrotin sulfate proteoglycan.  
     
     
         33 . The method of  claim 32 , wherein the one or more molecules is phosphocan, versican, neurocan, NG2, or neuroglycan C/NGC.  
     
     
         34 . The method of  claim 27 , wherein the one or more molecules is a syndecan.  
     
     
         35 . The method of  claim 34 , wherein the one or more molecules is syndecan-3.  
     
     
         36 . The method of  claim 27 , wherein the one or more molecules is adenylate cyclase 8.  
     
     
         37 . The method of  claim 27 , wherein the one or more molecules is selected from the group consisting of pleiotrophin, platelet-derived growth factor, NEL-like 1, neuralin 1, BMP2 (a Dpp homologue), OP-1, chromoganin B (secretogranin 1), or secretogranin II (chromogranin C).  
     
     
         38 . The method of  claim 37 , wherein one or more molecules is pleiotrophin.  
     
     
         39 . The method of  claim 37 , wherein the one or more molecules is NEL-like 1.  
     
     
         40 . The method of  claim 37 , wherein the one or more molecules is neuralin 1.  
     
     
         41 . The method of  claim 27 , wherein the one or molecules is a receptor tyrosine kinase.  
     
     
         42 . The method of  claim 27 , wherein the one or more molecules is platelet-derived growth factor receptor, cannabinoid receptor 1, G protein-coupled receptor 19, activated p21cdc42Hs kinase, or transmembrane 4 superfamily member 2.  
     
     
         43 . The method of  claim 27 , wherein the one or more molecules is GABA A receptor, glycine receptor beta, glutamate receptor ionotrophic AMPA 2, or glutamate receptor iontropic kainate 1.  
     
     
         44 . The method of  claim 27 , wherein one or more molecules is zinc finger DAZ interacting protein 1.  
     
     
         45 . The method of  claim 27 , wherein the neural progenitor cells are from a post-natal human.  
     
     
         46 . The method of  claim 27 , wherein the neural progenitor cells are from an adult human.  
     
     
         47 . The method of  claim 27 , wherein the condition is modulated by oligodendrocyte progenitor mobilization, division, proliferation, differentiation, and/or self-maintenance.  
     
     
         48 . The method of  claim 27 , wherein the condition is modulated by oligodendrocyte maturation, differentiation, myelin production, and/or axonal myelination.  
     
     
         49 . The method of  claim 27 , wherein the condition is selected from the group consisting of the pediatric leukodystrophies, the lysomal storage diseases, congenital dysmyelination, cerebral palsy, inflammatory demyelination, post-infectious and post-vaccinial leukoencephalitis, radiation- or chemotherapy-induced white matter damage, and vascular demyelination.  
     
     
         50 . A method differentiating oligodendrocyte progenitor cells to oligodendrocytes, said method comprising: 
 administering an inhibitor of sterol synthesis under conditions effective to differentiate oligodendrocyte progenitor cells to oligodendrocytes.    
     
     
         51 . The method of  claim 50 , wherein the inhibitor of sterol synthesis is selected from the group consisting of lovastatin, simvastatin, atorvastatin, pravastatin, fluvastatin, cerivastatin, and rosuvastatin.  
     
     
         52 . The method of  claim 50 , wherein the oligodendrocyte progenitor cells are from a post-natal human.  
     
     
         53 . The method of  claim 50 , wherein the oligodendrocyte progenitor cells are from an adult human.  
     
     
         54 . The method of  claim 50 , wherein the oligodendrocyte progenitor cells are from a fetal human.