Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells.
Our laboratory is working with the human NTera2/D1 (NT2) cell line, which has properties similar to those of progenitor cells in the central nervous system (CNS). These neural-like precursor cells can differentiate into all three major lineages, neurons, astrocytes, and oligodendrocytes. The pure neuronal population, hNT neurons, possess characteristics of dopamine (DA) cells. First, we analyzed whether the retinoic acid (RA)-treated hNT neurons and the NT2 precursor cells expressed two transcription factors required for development of the midbrain DA neurons. We report that NT2 cells endogenously expressed Engrailed-1 and Ptx3, whereas RA-treated hNT neurons did not express Engrailed-1 or Ptx3. Next we examined the influence of lithium treatment on Engrailed-1 and Ptx3 as well as another critical transcription factor, Nurr1. Previous research has shown that lithium can mimic the Wnt pathway, which is important for the induction of these transcription factors. Finally, we investigated the effect of lithium treatment on the viability and proliferation of NT2 cells, because lithium has been shown to stimulate neurogenesis in adult neural precursors. Lithium treatment increased the viability and proliferation of NT2 cells. The expression of transcription factors essential for the induction and maintenance of the DA phenotype was not increased in NT2 after lithium treatment. We conclude that the NT2 cell line is an excellent in vitro model system for studying the influence of pharmalogical agents on proliferation, differentiation, and apoptosis of a human neural progenitor cell line.
Misiuta
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IE
Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, Florida, USA.
Saporta
S
S
Sanberg
P R
PR
Zigova
T
T
Willing
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AE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008094:Lithium / Q000494:pharmacology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D000683:Serum Amyloid P-Component / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism; D000099153:Pentraxins
D000970:Antineoplastic Agents; D002097:C-Reactive Protein; D004268:DNA-Binding Proteins; D004298:Dopamine; D038362:Glycogen Synthase Kinase 3; D018398:Homeodomain Proteins; D008094:Lithium; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D000683:Serum Amyloid P-Component; D014157:Transcription Factors; D014212:Tretinoin; D051176:beta Catenin; D000099153:Pentraxins; C513076:EN1 protein, human; C539882:NR4A2 protein, human