Neuroscience 2002 Abstract
| Presentation Number: | 429.11 |
|---|---|
| Abstract Title: | Induced Nurr1 expression in ROSA26-engineered embryonic stem cells up-regulates dopaminergic marker gene expression in a non-neural cellular phenotype. |
| Authors: |
Sonntag, K. C.*1
; Chung, S.1,2
; Andersson, T. M.3
; Park, J. J.2
; Kim, D. W.2
; Cooper, O.1
; Bj÷rklund, L.1
; Kim, K. S.2
; Isacson, O.1
1Neuroregen. Lab., McLean Hospital, Belmont, MA 2Mol. Neurobiol. Lab., McLean Hospital, Belmont, MA 3Ctr Genomics & Bioinformatics, Karolinska Institute, Stockholm, Sweden |
| Primary Theme and Topics |
Development - Transplantation and Regeneration -- Transplantation |
| Session: |
429. Transplantation and regeneration: transplantation III Poster |
| Presentation Time: | Tuesday, November 5, 2002 10:00 AM-11:00 AM |
| Location: | Hall A2-B3 B-89 |
| Keywords: | embryonic stem cells, Tet system, Nurr1, in vitro differentiation |
Constitutive overexpression of the transcription factor Nurr1 in pluripotent embryonic stem (ES) cells enhances the development of tyrosine hydroxylase (TH) pos. midbrain dopaminergic (DA) neurons in vitro (S. Chung, SFN 2001 mtg. abstr.#14452). To determine the effects of Nurr1 expression at different stages of cell differentiation, we generated inducible Nurr1-expressing J1-rtTA ES cell clones, which express the reverse transactivator (rtTA) of the Tet-System from the ROSA26 locus and characterized them in in vitro differentitation assays. We found that the rtTA-recombinant J1 cells developed into fewer neurons including the TH+ subtype when compared to naïve J1 ES cells. However, the pattern of marker gene expression specific for early CNS (Otx1, Otx2, GBX2, En-1), germlayers (CK-17, GATA4, HNF-4, Brachyury) and midbrain DA (Pitx3, AADC, Calbindin, DAT) were similar between the J1 ES cells analyzed. In this system, the induction of Nurr1 expression at different stages during cell differentiation led to the development of an atypical TH+ cell population and the up-regulation of midbrain DA-specific markers, i.e. TH and DAT. Development of other neuronal phenotypes and the expression pattern of early CNS and other neuronal markers were not altered. Our data demonstrate that Nurr1 can specifically activate the TH and DAT genes independent from the development of a neural phenotype.
Supported by Udall Parkinson’s Dis. Ctr of Excellence grants P50 NS39793 and DAMD 17-01-1-0762.
Supported by Udall Parkinson’s Dis. Ctr of Excellence grants P50 NS39793 and DAMD 17-01-1-0762.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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