Expression of RALDHs (ALDH1As) and CYP26s in human tissues and during the neural differentiation of P19 embryonal carcinoma stem cell

Retinoic acid (RA) plays a critical role in embryonic development and function maintenance of vital organs in adult. Subtle regulation of RA signaling is relied on spatio-temporal control of RA synthesis and catabolism. In this study, we investigated the expression patterns of RA synthetases RALDHs and metabolic enzymes CYP26s in multiple human tissues, and this study revealed unique expression pattern for every isoform from these two enzyme families. And it was worth noting that there were evident differences between fetal brain and adult brain in the expression of RALDHs and CYP26s. To investigate the dynamic expression of RALDH isoforms and CYP26 isoforms during neural differentiation, we applied a P19 embryonal carcinoma stem cell neural differentiation model. And during P19 cell neural differentiation induced by all trans-retinoic acid (ATRA) and cell aggregate formation, RALDH1, RALDH2, CYP26A1, and CYP26B1 could be notably upregulated by ATRA, and keeping the high-level expression of RALDH1 and RALDH2 was dependent on the further neural differentiation, but not continuous ATRA induction. RALDH3 transcription could not be directly induced by ATRA, and obvious upregulation of its transcription initiated at the late stage of ATRA induction or after the removement of ATRA implied its neural differentiation-dependent expression pattern. CYP26C1 transcription was significantly repressed by ATRA, and this downregulation also showed a neural differentiation-dependent pattern, in respect that CYP26C1 expression was kept in low-level even after the withdrawal of ATRA.