Comparative transcriptomics reveals human-specific cortical features

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular and molecular organization. Human, chimpanzee, and gorilla MTG showed highly similar cell type composition and laminar organization, and a large shift in proportions of deep layer intratelencephalic-projecting neurons compared to macaque and marmoset. Species differences in gene expression generally mirrored evolutionary distance and were seen in all cell types, although chimpanzees were more similar to gorillas than humans, consistent with faster divergence along the human lineage. Microglia, astrocytes, and oligodendrocytes showed accelerated gene expression changes compared to neurons or oligodendrocyte precursor cells, indicating either relaxed evolutionary constraints or positive selection in these cell types. Only a few hundred genes showed human-specific patterning in all or specific cell types, and were significantly enriched near human accelerated regions (HARs) and conserved deletions (hCONDELS) and in cell adhesion and intercellular signaling pathways. These results suggest that relatively few cellular and molecular changes uniquely define adult human cortical structure, particularly by affecting circuit connectivity and glial cell function.

Authors 41

1. Nikolas L. Jorstad

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science

   Seattle, WA, 9809

2. Janet H. T. Song

   Boston Children's Hospital · Howard Hughes Medical Institute · Harvard University

   Affiliation as printed

   Division of Genetics and Genomics and HHMI, Boston Children’s Hospital, Harvard Medical School

   Boston, MA

   Division of Genetics and Genomics and HHMI, Boston Children's Hospital, Harvard Medical School

3. David Exposito-Alonso

   Boston Children's Hospital · Howard Hughes Medical Institute · Harvard University

   Affiliation as printed

   Division of Genetics and Genomics and HHMI, Boston Children’s Hospital, Harvard Medical School

   Boston, MA

   Division of Genetics and Genomics and HHMI, Boston Children's Hospital, Harvard Medical School

4. Hamsini Suresh

   Cold Spring Harbor Laboratory

   Affiliation as printed

   Cold Spring Harbor Laboratory

   Cold Spring Harbor, NY

5. Fenna M. Krienen

   Harvard University

   Affiliation as printed

   Department of Genetics, Harvard Medical School

   77 Avenue Louis Pasteur Boston MA 02115

6. Anna Marie Yanny

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science

   Seattle, WA, 9809

7. Jennie Close

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science

   Seattle, WA, 9809

8. Emily C. Gelfand

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science

   Seattle, WA, 9809

9. Kyle J. Travaglini

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science

   Seattle, WA, 9809

10. Soumyadeep Basu Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center · Delft University of Technology

    Affiliation as printed

    Computer Graphics and Visualization Group, Delft University of Technology

    LKEB, Dept of Radiology, Leiden University Medical Center

    Delft, The Netherlands

    Leiden, The Netherlands

11. Darren Bertagnolli

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

12. Megan Crow

    Cold Spring Harbor Laboratory

    Affiliation as printed

    Cold Spring Harbor Laboratory

    Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory

    Cold Spring Harbor, NY

13. Song‐Lin Ding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

14. Jeroen Eggermont Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    LKEB, Dept of Radiology, Leiden University Medical Center

    Leiden, The Netherlands

15. Alexandra Glandon

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

16. Jeff Goldy

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

17. Thomas Kroes Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    LKEB, Dept of Radiology, Leiden University Medical Center

    Leiden, The Netherlands

18. Brian Long

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

19. Delissa McMillen

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

20. Trangthanh H. Pham

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

21. Christine Rimorin

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

22. Kimberly Siletti

    Karolinska Institutet

    Affiliation as printed

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet

    Stockholm, Sweden

23. Saroja Somasundaram

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

24. Michael Tieu

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

25. Amy Torkelson

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

26. Katelyn Ward

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

27. Guoping Feng

    Broad Institute · McGovern Institute for Brain Research · Stanley Center for Psychiatric Research · Massachusetts Institute of Technology

    Affiliation as printed

    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology

    McGovern Institute for Brain Research, Massachusetts Institute of Technology

    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard

    Cambridge, Massachusetts 0213

    Cambridge, Massachusetts 02139

    Cambridge, Massachusetts 02142

28. William Donald Hopkins

    The University of Texas MD Anderson Cancer Center

    Affiliation as printed

    Keeling Center for Comparative Medicine and Research, University of Texas, MD Anderson Cancer Center

    Houston, TX

29. Thomas Höllt

    Delft University of Technology

    Affiliation as printed

    Computer Graphics and Visualization Group, Delft University of Technology

    Delft, The Netherlands

30. Christopher Dirk Keene

    University of Washington

    Affiliation as printed

    Department of Laboratory Medicine and Pathology, University of Washington

    Seattle, WA, USA

31. Sten Linnarsson

    Karolinska Institutet

    Affiliation as printed

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet

    Stockholm, Sweden

32. Steven A. McCarroll

    Broad Institute · Harvard University

    Affiliation as printed

    Broad Institute of MIT and Harvard

    Department of Genetics, Harvard Medical School

    77 Avenue Louis Pasteur Boston MA 02115

    Cambridge, MA 022

33. Boudewijn P. F. Lelieveldt Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center · Delft University of Technology

    Affiliation as printed

    LKEB, Dept of Radiology, Leiden University Medical Center

    Pattern Recognition and Bioinformatics group, Delft University of Technology

    Delft, The Netherlands

    Leiden, The Netherlands

34. Chet C. Sherwood

    George Washington University

    Affiliation as printed

    Department of Anthropology, The George Washington University

    Washington, DC

35. Kimberly A. Smith

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

36. Christopher A. Walsh

    Boston Children's Hospital · Howard Hughes Medical Institute · Harvard University

    Affiliation as printed

    Division of Genetics and Genomics and HHMI, Boston Children’s Hospital, Harvard Medical School

    Boston, MA

    Division of Genetics and Genomics and HHMI, Boston Children's Hospital, Harvard Medical School

37. Alexander Dobin

    Cold Spring Harbor Laboratory

    Affiliation as printed

    Cold Spring Harbor Laboratory

    Cold Spring Harbor, NY

38. Jesse A Gillis

    University of Toronto

    Affiliation as printed

    Department of Physiology, University of Toronto

    Toronto, Canada

39. Ed S. Lein

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

40. Rebecca D. Hodge corresponding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809

41. Trygve E. Bakken corresponding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science

    Seattle, WA, 9809