RT Journal Article
SR Electronic
T1 Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 380758
DO 10.1101/380758
A1 EE Burke
A1 JG Chenoweth
A1 JH Shin
A1 L Collado-Torres
A1 SK Kim
A1 N Micali
A1 Y Wang
A1 RE Straub
A1 DJ Hoeppner
A1 HY Chen
A1 A Lescure
A1 K Shibbani
A1 GR Hamersky
A1 BN Phan
A1 WS Ulrich
A1 C Valencia
A1 A Jaishankar
A1 AJ Price
A1 A Rajpurohit
A1 SA Semick
A1 R Bürli
A1 JC Barrow
A1 DJ Hiler
A1 SC Page
A1 K Martinowich
A1 TM Hyde
A1 JE Kleinman
A1 KF Berman
A1 JA Apud
A1 AJ Cross
A1 NJ Brandon
A1 DR Weinberger
A1 BJ Maher
A1 RDG McKay
A1 AE Jaffe
YR 2018
UL http://biorxiv.org/content/early/2018/07/31/380758.abstract
AB Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across nine time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells that were validated using electrophysiology. We identified widespread changes in the expression of individual transcript features and their splice variants, gene networks, and global patterns of transcription. We next demonstrated that co-culturing human NPCs with rodent astrocytes resulted in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without potentially disruptive cell sorting. We lastly developed and validated a computational tool to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue, which were maturationally heterogeneous but contained subsets of cells most akin to adult human neurons.