RT Journal Article
SR Electronic
T1 Enhanced maturation of human stem cell derived interneurons by mTOR activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 777714
DO 10.1101/777714
A1 Jianhua Chu
A1 Megan L. Fitzgerald
A1 Neha Sehgal
A1 William Manley
A1 Shane Fitzgerald
A1 Harrison Naung
A1 Ethan M. Goldberg
A1 Stewart A. Anderson
YR 2019
UL http://biorxiv.org/content/early/2019/11/20/777714.abstract
AB The use of stem cell derived neurons for cell-based therapies is limited by a protracted maturation. We present a novel approach for accelerating the post-mitotic maturation of human stem cell derived interneurons via the activation of mTOR signaling. Lox sites were placed within PTEN, a key mTOR inhibitor, in a cortical interneuron (CIn) reporter line. Following directed differentiation and purification by FACS, the CIns were exposed to Cre-expressing lentivirus, then transplanted into mouse neocortex or plated onto cultured rat neocortex. Input synaptogenesis and dendritogenesis was greatly enhanced in the PTEN-deleted CIns. Whole-cell recording of the PTEN-deleted CIns in slices of transplanted neocortex revealed multiple indices of enhanced maturation. Finally, we observed similar effects using transient, doxycycline-inducible activation of AKT. We thus present an inducible, reversible approach for accelerating the maturation of human stem cell derived CIns, and to study the influences of this disease-related signaling system in human neurons.