Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs.

Autor: Burke EE; Lieber Institute for Brain Development, Baltimore, MD, USA., Chenoweth JG; Lieber Institute for Brain Development, Baltimore, MD, USA., Shin JH; Lieber Institute for Brain Development, Baltimore, MD, USA., Collado-Torres L; Lieber Institute for Brain Development, Baltimore, MD, USA., Kim SK; Lieber Institute for Brain Development, Baltimore, MD, USA., Micali N; Lieber Institute for Brain Development, Baltimore, MD, USA., Wang Y; Lieber Institute for Brain Development, Baltimore, MD, USA., Colantuoni C; Lieber Institute for Brain Development, Baltimore, MD, USA., Straub RE; Lieber Institute for Brain Development, Baltimore, MD, USA., Hoeppner DJ; Lieber Institute for Brain Development, Baltimore, MD, USA., Chen HY; Lieber Institute for Brain Development, Baltimore, MD, USA., Sellers A; Lieber Institute for Brain Development, Baltimore, MD, USA., Shibbani K; Lieber Institute for Brain Development, Baltimore, MD, USA., Hamersky GR; Lieber Institute for Brain Development, Baltimore, MD, USA., Diaz Bustamante M; Lieber Institute for Brain Development, Baltimore, MD, USA., Phan BN; Lieber Institute for Brain Development, Baltimore, MD, USA., Ulrich WS; Lieber Institute for Brain Development, Baltimore, MD, USA., Valencia C; Lieber Institute for Brain Development, Baltimore, MD, USA., Jaishankar A; Lieber Institute for Brain Development, Baltimore, MD, USA., Price AJ; Lieber Institute for Brain Development, Baltimore, MD, USA.; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA., Rajpurohit A; Lieber Institute for Brain Development, Baltimore, MD, USA., Semick SA; Lieber Institute for Brain Development, Baltimore, MD, USA., Bürli RW; Neuroscience, IMED Biotech Unit, AstraZeneca, Cambridge, UK., Barrow JC; Lieber Institute for Brain Development, Baltimore, MD, USA., Hiler DJ; Lieber Institute for Brain Development, Baltimore, MD, USA., Page SC; Lieber Institute for Brain Development, Baltimore, MD, USA., Martinowich K; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA., Hyde TM; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Berman KF; Clinical and Translational Neuroscience Branch, NIMH Intramural Research Program, Bethesda, MD, USA., Apud JA; Clinical and Translational Neuroscience Branch, NIMH Intramural Research Program, Bethesda, MD, USA., Cross AJ; Neuroscience, IMED Biotech Unit, AstraZeneca, Boston, MA, USA., Brandon NJ; Neuroscience, IMED Biotech Unit, AstraZeneca, Boston, MA, USA., Weinberger DR; Lieber Institute for Brain Development, Baltimore, MD, USA.; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Maher BJ; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA., McKay RDG; Lieber Institute for Brain Development, Baltimore, MD, USA. ronald.mckay@libd.org., Jaffe AE; Lieber Institute for Brain Development, Baltimore, MD, USA. andrew.jaffe@libd.org.; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. andrew.jaffe@libd.org.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. andrew.jaffe@libd.org.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA. andrew.jaffe@libd.org.; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. andrew.jaffe@libd.org.; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. andrew.jaffe@libd.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Jan 23; Vol. 11 (1), pp. 462. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1038/s41467-019-14266-z
Abstrakt: 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.
Databáze: MEDLINE