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, Ba Doi N. Phan, William S. Ulrich, Cristian Valencia, Amritha Jaishankar, Amanda J. PriceAnandita 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, Andrew E. Jaffe

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number462
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Burke, E. E., Chenoweth, J. G., Shin, J. H., Collado-Torres, L., Kim, S. K., Micali, N., Wang, Y., Colantuoni, C., Straub, R. E., Hoeppner, D. J., Chen, H. Y., Sellers, A., Shibbani, K., Hamersky, G. R., Diaz Bustamante, M., Phan, B. D. N., Ulrich, W. S., Valencia, C., Jaishankar, A., ... Jaffe, A. E. (2020). Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs. Nature communications, 11(1), [462]. https://doi.org/10.1038/s41467-019-14266-z