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Structurally Conserved Primate lncRNAs Are Transiently Expressed During Human Cortical Differentiation and Influence Cell Type Specific Genes

59 Pages Posted: 13 Apr 2018 Publication Status: Review Complete

See all articles by Andrew R. Field

Andrew R. Field

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Frank M. J. Jacobs

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

Ian T. Fiddes

University of California, Santa Cruz - Genomics Institute

Alex P. R. Phillips

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

Andrea M. Reyes-Ortiz

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

Erin LaMontagne

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

Lila Whitehead

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Vincent Meng

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Jimi L. Rosenkrantz

Howard Hughes Medical Institute (HHMI) - Chevy Chase

Maximilian Haeussler

University of California, Santa Cruz - Genomics Institute

Sol Katzman

University of California, Santa Cruz - Genomics Institute

Sofie R. Salama

University of California, Santa Cruz - Genomics Institute; Howard Hughes Medical Institute (HHMI) - Chevy Chase

David Haussler

University of California, Santa Cruz - Howard Hughes Medical Institute

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Abstract

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 noncoding 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.

Suggested Citation

Field, Andrew R. and Jacobs, Frank M. J. and Fiddes, Ian T. and Phillips, Alex P. R. and Reyes-Ortiz, Andrea M. and LaMontagne, Erin and Whitehead, Lila and Meng, Vincent and Rosenkrantz, Jimi L. and Haeussler, Maximilian and Katzman, Sol and Salama, Sofie R. and Haussler, David, Structurally Conserved Primate lncRNAs Are Transiently Expressed During Human Cortical Differentiation and Influence Cell Type Specific Genes (2018). Available at SSRN: https://ssrn.com/abstract=3155810 or http://dx.doi.org/10.2139/ssrn.3155810
This version of the paper has not been formally peer reviewed.

Andrew R. Field

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Santa Cruz, CA 95064
United States

Frank M. J. Jacobs

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

1156 High Street
335 Baskin Engineering Building
Santa Cruz, CA 95064
United States

Ian T. Fiddes

University of California, Santa Cruz - Genomics Institute

1156 High St
Santa Cruz, CA
United States

Alex P. R. Phillips

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

1156 High Street
335 Baskin Engineering Building
Santa Cruz, CA 95064
United States

Andrea M. Reyes-Ortiz

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

1156 High Street
335 Baskin Engineering Building
Santa Cruz, CA 95064
United States

Erin LaMontagne

University of California, Santa Cruz - Department of Biomolecular Engineering (BME)

1156 High Street
335 Baskin Engineering Building
Santa Cruz, CA 95064
United States

Lila Whitehead

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Santa Cruz, CA 95064
United States

Vincent Meng

University of California, Santa Cruz - Department of Molecular, Cell, and Developmental Biology

Santa Cruz, CA 95064
United States

Jimi L. Rosenkrantz

Howard Hughes Medical Institute (HHMI) - Chevy Chase

4000 Jones Bridge Road
Chevy Chase, MD 20815-6789
United States

Maximilian Haeussler

University of California, Santa Cruz - Genomics Institute

1156 High St
Santa Cruz, CA
United States

Sol Katzman

University of California, Santa Cruz - Genomics Institute

1156 High St
Santa Cruz, CA
United States

Sofie R. Salama (Contact Author)

University of California, Santa Cruz - Genomics Institute

1156 High St
Santa Cruz, CA
United States

Howard Hughes Medical Institute (HHMI) - Chevy Chase

United States

David Haussler

University of California, Santa Cruz - Howard Hughes Medical Institute ( email )

Santa Cruz, CA 95604
United States