Comparative transcriptomics reveals human-specific cortical features

Science, vol. 382, pp. eade9516

Abstract

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.

Authors 43

1. Nikolas L. Jorstad corresponding

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science, Seattle, WA 98109, USA

2. Janet H. T. Song corresponding

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

   Affiliation as printed

   Allen Discovery Center for Human Brain Evolution, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA

   Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA

   Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA

   Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USA

   Allen Discovery Center for Human Brain Evolution, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA

   Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA

   Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA

3. David Exposito-Alonso corresponding

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

   Affiliation as printed

   Allen Discovery Center for Human Brain Evolution, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA

   Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA

   Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA

   Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USA

   Allen Discovery Center for Human Brain Evolution, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA

   Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA

   Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA

4. Hamsini Suresh

   Cold Spring Harbor Laboratory

   Affiliation as printed

   Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

5. Nathan Castro-Pacheco

   Cold Spring Harbor Laboratory

   Affiliation as printed

   Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

6. Fenna M. Krienen

   Harvard University

   Affiliation as printed

   Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

7. Anna Marie Yanny

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science, Seattle, WA 98109, USA

8. Jennie Close

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science, Seattle, WA 98109, USA

9. Emily C. Gelfand

   Allen Institute for Brain Science

   Affiliation as printed

   Allen Institute for Brain Science, Seattle, WA 98109, USA

10. Brian Long

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

11. Stephanie C. Seeman

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

12. Kyle J. Travaglini

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

13. 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, Delft, Netherlands

    LKEB, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

14. Darren Bertagnolli

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

15. Megan Crow

    Cold Spring Harbor Laboratory

    Affiliation as printed

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

    Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

16. Song‐Lin Ding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

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

    Leiden University Medical Center

    Affiliation as printed

    LKEB, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

18. Alexandra Glandon

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

19. Jeff Goldy

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

20. Katelyn Kiick

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

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

    Leiden University Medical Center

    Affiliation as printed

    LKEB, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

22. Delissa McMillen

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

23. Trangthanh H. Pham

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

24. Christine Rimorin

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

25. Kimberly Siletti

    Karolinska Institutet

    Affiliation as printed

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

26. Saroja Somasundaram

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

27. Michael Tieu

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

28. Amy Torkelson

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

29. 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, Cambridge, MA 02139, USA

    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

30. 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 78602, USA

31. Thomas Höllt

    Delft University of Technology

    Affiliation as printed

    Computer Graphics and Visualization Group, Delft University of Technology, Delft, Netherlands

32. Christopher Dirk Keene

    University of Washington

    Affiliation as printed

    Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA

33. Sten Linnarsson

    Karolinska Institutet

    Affiliation as printed

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

34. Steven A. McCarroll

    Broad Institute · Harvard University

    Affiliation as printed

    Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

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

    Leiden University Medical Center · Delft University of Technology

    Affiliation as printed

    LKEB, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

    Pattern Recognition and Bioinformatics Group, Delft University of Technology, Delft, Netherlands

36. Chet C. Sherwood

    George Washington University

    Affiliation as printed

    Department of Anthropology, The George Washington University, Washington, DC 20037, USA

37. Kimberly A. Smith

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

38. Christopher A. Walsh

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

    Affiliation as printed

    Allen Discovery Center for Human Brain Evolution, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA

    Department of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA

    Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA

    Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA 02115, USA

    Allen Discovery Center for Human Brain Evolution, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA

    Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA

    Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA

39. Alexander Dobin

    Cold Spring Harbor Laboratory

    Affiliation as printed

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

40. Jesse A Gillis

    University of Toronto

    Affiliation as printed

    Department of Physiology, University of Toronto, Toronto, ON, Canada

41. Ed S. Lein

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

42. Rebecca D. Hodge corresponding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA

43. Trygve E. Bakken corresponding

    Allen Institute for Brain Science

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA 98109, USA