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Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell type specific genes

Andrew R. Field, Frank M.J. Jacobs, Ian T. Fiddes, Alex P.R. Phillips, Andrea M. Reyes-Ortiz, Erin LaMontagne, Lila Whitehead, Vincent Meng, Jimi L. Rosenkrantz, Maximillian Haeussler, Sol Katzman, Sofie R. Salama, David Haussler
doi: https://doi.org/10.1101/232553
Andrew R. Field
1Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America,
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Frank M.J. Jacobs
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Ian T. Fiddes
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Alex P.R. Phillips
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Andrea M. Reyes-Ortiz
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Erin LaMontagne
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Lila Whitehead
1Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Vincent Meng
1Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Jimi L. Rosenkrantz
4Howard Hughes Medical Institute, University of California, Santa Cruz, Santa Cruz, California, United States of America
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Maximillian Haeussler
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Sol Katzman
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
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Sofie R. Salama
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
4Howard Hughes Medical Institute, University of California, Santa Cruz, Santa Cruz, California, United States of America
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David Haussler
2Genomics Institute, University of California Santa Cruz, Santa Cruz, California, United States of America,
3Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America,
4Howard Hughes Medical Institute, University of California, Santa Cruz, Santa Cruz, California, United States of America
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SUMMARY

The cerebral cortex has expanded in size and complexity in primates, yet the underlying molecular mechanisms are obscure. We generated cortical organoids from human, chimpanzee, orangutan, and rhesus pluripotent stem cells and sequenced their transcriptomes at weekly time points for comparative analysis. We used transcript structure and expression conservation to discover thousands of expressed long non-coding RNAs (lncRNAs). Of 2,975 human, multi-exonic lncRNAs, 2,143 were structurally conserved to chimpanzee, 1,731 to orangutan, and 1,290 to rhesus. 386 human lncRNAs were transiently expressed (TrEx) and a similar expression pattern was often observed in great apes (46%) and rhesus (31%). Many TrEx lncRNAs were associated with neuroepithelium, radial glia, or Cajal-Retzius cells by single cell RNA-sequencing. 3/8 tested by ectopic expression showed ≥2-fold effects on neural genes. This rich resource of primate expression data in early cortical development provides a framework for identifying new, potentially functional lncRNAs.

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  • ↵5 Senior and Corresponding Authors

  • ↵6 Lead contact

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 12, 2017.
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Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell type specific genes
Andrew R. Field, Frank M.J. Jacobs, Ian T. Fiddes, Alex P.R. Phillips, Andrea M. Reyes-Ortiz, Erin LaMontagne, Lila Whitehead, Vincent Meng, Jimi L. Rosenkrantz, Maximillian Haeussler, Sol Katzman, Sofie R. Salama, David Haussler
bioRxiv 232553; doi: https://doi.org/10.1101/232553
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Structurally conserved primate lncRNAs are transiently expressed during human cortical differentiation and influence cell type specific genes
Andrew R. Field, Frank M.J. Jacobs, Ian T. Fiddes, Alex P.R. Phillips, Andrea M. Reyes-Ortiz, Erin LaMontagne, Lila Whitehead, Vincent Meng, Jimi L. Rosenkrantz, Maximillian Haeussler, Sol Katzman, Sofie R. Salama, David Haussler
bioRxiv 232553; doi: https://doi.org/10.1101/232553

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