Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Emily E. Burke, Joshua G. Chenoweth, Joo Heon Shin, Leonardo Collado-Torres, Suel-Kee Kim, Nicola Micali, Yanhong Wang, Carlo Colantuoni, Richard E. Straub, Daniel J. Hoeppner, Huei-Ying Chen, Alana Sellers, Kamel Shibbani, Gregory R. Hamersky, Marcelo Diaz Bustamante, BaDoi N. Phan, William S. Ulrich, Cristian Valencia, Amritha Jaishankar, Amanda J. Price, Anandita Rajpurohit, Stephen A. Semick, Roland W. Bürli, James C. Barrow, Daniel J. Hiler, Stephanie C. Page, Keri Martinowich, Thomas M. Hyde, Joel E. Kleinman, Karen F. Berman, Jose A. Apud, Alan J. Cross, Nicholas J. Brandon, Daniel R. Weinberger, Brady J. Maher, Ronald D. G. McKay () and Andrew E. Jaffe ()
Additional contact information
Emily E. Burke: Lieber Institute for Brain Development
Joshua G. Chenoweth: Lieber Institute for Brain Development
Joo Heon Shin: Lieber Institute for Brain Development
Leonardo Collado-Torres: Lieber Institute for Brain Development
Suel-Kee Kim: Lieber Institute for Brain Development
Nicola Micali: Lieber Institute for Brain Development
Yanhong Wang: Lieber Institute for Brain Development
Carlo Colantuoni: Lieber Institute for Brain Development
Richard E. Straub: Lieber Institute for Brain Development
Daniel J. Hoeppner: Lieber Institute for Brain Development
Huei-Ying Chen: Lieber Institute for Brain Development
Alana Sellers: Lieber Institute for Brain Development
Kamel Shibbani: Lieber Institute for Brain Development
Gregory R. Hamersky: Lieber Institute for Brain Development
Marcelo Diaz Bustamante: Lieber Institute for Brain Development
BaDoi N. Phan: Lieber Institute for Brain Development
William S. Ulrich: Lieber Institute for Brain Development
Cristian Valencia: Lieber Institute for Brain Development
Amritha Jaishankar: Lieber Institute for Brain Development
Amanda J. Price: Lieber Institute for Brain Development
Anandita Rajpurohit: Lieber Institute for Brain Development
Stephen A. Semick: Lieber Institute for Brain Development
Roland W. Bürli: Neuroscience, IMED Biotech Unit, AstraZeneca
James C. Barrow: Lieber Institute for Brain Development
Daniel J. Hiler: Lieber Institute for Brain Development
Stephanie C. Page: Lieber Institute for Brain Development
Keri Martinowich: Lieber Institute for Brain Development
Thomas M. Hyde: Lieber Institute for Brain Development
Joel E. Kleinman: Lieber Institute for Brain Development
Karen F. Berman: Clinical and Translational Neuroscience Branch, NIMH Intramural Research Program
Jose A. Apud: Clinical and Translational Neuroscience Branch, NIMH Intramural Research Program
Alan J. Cross: Neuroscience, IMED Biotech Unit, AstraZeneca
Nicholas J. Brandon: Neuroscience, IMED Biotech Unit, AstraZeneca
Daniel R. Weinberger: Lieber Institute for Brain Development
Brady J. Maher: Lieber Institute for Brain Development
Ronald D. G. McKay: Lieber Institute for Brain Development
Andrew E. Jaffe: Lieber Institute for Brain Development

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.

Date: 2020
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DOI: 10.1038/s41467-019-14266-z

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