Comprehensive analysis of microRNA expression in regionalized human neural progenitor cells reveals microRNA-10 as a caudalizing factor

MicroRNAs (miRNAs) have been implicated in regulating multiple processes during brain development in various species. However, the function of miRNAs in human brain development remains largely unexplored. Here, we provide a comprehensive analysis of miRNA expression of regionalized neural progenitor cells derived from human embryonic stem cells and human fetal brain. We found mir-92b-3p and mir-130b-5p to be specifically associated with neural progenitors and several miRNAs that display both age-specific and region-specific expression patterns. Among these miRNAs, we identified miR-10 to be specifically expressed in the human hindbrain and spinal cord, while absent from rostral regions. We found that miR-10 regulates a large number of genes enriched for functions including transcription, actin cytoskeleton and ephrin receptor signaling. When overexpressed, miR-10 influences caudalization of human neural progenitors cells. Together, these data confirms a role for miRNAs in establishing different human neural progenitor populations. This data set also provides a comprehensive resource for future studies investigating the functional role of different miRNAs in human brain development. Overall design: Human embryonic stem cells (hESCs) were transduced with lentiviral vectors expressing either miR10a-GFP or miR10b-GFP. The expression of the vectors is Tet-regulated and they will only be expressed in the presence of Doxycycline. In order to detect direct targets of the miR10a and miR10b, we differentiated the trasduced hESCs for 14 days, and added doxycycline to only half of the groups - resulting in groups that are overexpressing miR10a or miR10b and some groups that are not overexpressing these miRNAs.

12

Jönsson ME, Nelander Wahlestedt J, Åkerblom M, Kirkeby A, Malmevik J, Brattaas PL, Jakobsson J, Parmar M