The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model

Kiyohito Murai, Guoqiang Sun, Peng Ye, E. Tian, Su Yang, Qi Cui, Guihua Sun, Daniel Trinh, Olivia Sun, Teresa Hong, Zhexing Wen, Markus Kalkum, Arthur D. Riggs, Hongjun Song, Guo-li Ming and Yanhong Shi ()
Additional contact information
Kiyohito Murai: Cancer Center, Beckman Research Institute of City of Hope
Guoqiang Sun: Cancer Center, Beckman Research Institute of City of Hope
Peng Ye: Cancer Center, Beckman Research Institute of City of Hope
E. Tian: Cancer Center, Beckman Research Institute of City of Hope
Su Yang: Cancer Center, Beckman Research Institute of City of Hope
Qi Cui: Cancer Center, Beckman Research Institute of City of Hope
Guihua Sun: Beckman Research Institute of City of Hope
Daniel Trinh: Cancer Center, Beckman Research Institute of City of Hope
Olivia Sun: Cancer Center, Beckman Research Institute of City of Hope
Teresa Hong: Beckman Research Institute of City of Hope
Zhexing Wen: Institute for Cell Engineering, Johns Hopkins University School of Medicine
Markus Kalkum: Beckman Research Institute of City of Hope
Arthur D. Riggs: Beckman Research Institute of City of Hope
Hongjun Song: Institute for Cell Engineering, Johns Hopkins University School of Medicine
Guo-li Ming: Institute for Cell Engineering, Johns Hopkins University School of Medicine
Yanhong Shi: Cancer Center, Beckman Research Institute of City of Hope

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10965 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10965

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10965

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().