We verified this using hNPCs derived from a second individual (data not shown).
This was verified using hNPCs from a second individual (data not shown).
AhR-dependent gene transcription is inducible only in mNPCs, and not in hNPCs because of low abundance of AhR and ARNT transcripts and absence of AhR protein in human cells.
Comparison of mRNA expression levels between hNPCs and mNPCs showed that genes belonging to the AhR machinery and AhR-dependent genes were generally expressed in higher copy numbers/1,000 copies [beta]-actin in mNPCs than in hNPCs (Table 1).
Specifically, in this study we discovered that proliferation of hNPCs was not affected by AhR agonists (3-MC, TCDD) or the AhR antagonist MNF (Figure 1A-C), whereas proliferation of wild-type mNPCs was completely blocked by AhR antagonism (Figure ID-F).
That ERK-dependent pathways are also necessary for normal migration of hNPCs was recently shown by our group (Moors et al.
To address the underlying reason for the observed species-specific differences in response to AhR modulation between hNPCs and mNPCs, we quantified copy numbers of genes that belong to the AhR machinery as well as genes that are AhR regulated.
To shed light onto the effects caused by PBDE exposure in human developing brain cells, we studied their effects on the development of hNPCs in vitro.
1-10 [micro]M) are not cytotoxic for proliferating or differentiating hNPCs over a period of 2 weeks, as we demonstrated by different, independent methods [see Supplemental Material, Figures 1 and 2 (doi: 10.
In contrast to proliferation, both investigated PBDE congeners inhibit migration and differentiation of hNPCs significantly in a concentration-dependent manner (Figures 1 and 2).
These studies might be explained by the data generated in our experiments because the two PBDE congeners BDE-47 and -99 directly disturb migration and delay differentiation of hNPCs in vitro by endocrine disruption of cellular TH signaling.
BDE-47 exerts similar short-term effects on hNPCs (Gassmann K, Krause G, Dingemans M, Schreiber T, Abel J, Bergman A, et al.