A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

doi:10.1038/s41588-024-01990-6

. 2024 Nov 20.

doi: 10.1038/s41588-024-01990-6. Online ahead of print.

A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

Christina Steyn^{1

2}, Ruvimbo Mishi^{1

2}, Stephanie Fillmore^{1

2}, Matthijs B Verhoog^{1

2}, Jessica More^{1

2}, Ursula K Rohlwink^{2

3}, Roger Melvill³, James Butler^{2

4}, Johannes M N Enslin^{2

3}, Muazzam Jacobs^{2

5

6

7}, Tatjana Sauka-Spengler^{8

9}, Maria Greco¹⁰, Sadi Quiñones^{11

12}, Chris G Dulla¹¹, Joseph V Raimondo^{1

2

5}, Anthony Figaji^{2

3}, Dorit Hockman^{13

14}

Affiliations

¹ Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
² Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³ Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa.
⁴ Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁵ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁶ Division of Immunology, Department of Pathology University of Cape Town, Cape Town, South Africa.
⁷ National Health Laboratory Service, Cape Town, South Africa.
⁸ Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
⁹ Stowers Institute for Medical Research, Kansas City, MO, USA.
¹⁰ Single Cell Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
¹¹ Department of Neuroscience, Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
¹² Graduate School of Biomedical Science, Tufts University School of Medicine, Boston, MA, USA.
¹³ Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa. dorit.hockman@uct.ac.za.
¹⁴ Neuroscience Institute, University of Cape Town, Cape Town, South Africa. dorit.hockman@uct.ac.za.

PMID: 39567748
DOI: 10.1038/s41588-024-01990-6

A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

Christina Steyn et al. Nat Genet. 2024.

. 2024 Nov 20.

doi: 10.1038/s41588-024-01990-6. Online ahead of print.

Authors

Affiliations

¹ Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
² Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³ Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa.
⁴ Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁵ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁶ Division of Immunology, Department of Pathology University of Cape Town, Cape Town, South Africa.
⁷ National Health Laboratory Service, Cape Town, South Africa.
⁸ Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
⁹ Stowers Institute for Medical Research, Kansas City, MO, USA.
¹⁰ Single Cell Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
¹¹ Department of Neuroscience, Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
¹² Graduate School of Biomedical Science, Tufts University School of Medicine, Boston, MA, USA.
¹³ Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa. dorit.hockman@uct.ac.za.
¹⁴ Neuroscience Institute, University of Cape Town, Cape Town, South Africa. dorit.hockman@uct.ac.za.

PMID: 39567748
DOI: 10.1038/s41588-024-01990-6

Abstract

The human brain undergoes protracted postnatal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell-type-specific gene expression dynamics. Here, using single-nucleus RNA sequencing on temporal lobe tissue, including samples of African ancestry, we build a joint pediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics. We explore the differences between pediatric and adult cell subtypes, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in pediatric tissue. The resources we present here improve our understanding of the brain during its development and contribute to global efforts to build an inclusive brain cell map.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Update of

Cell type-specific gene expression dynamics during human brain maturation.
Steyn C, Mishi R, Fillmore S, Verhoog MB, More J, Rohlwink UK, Melvill R, Butler J, Enslin JMN, Jacobs M, Sauka-Spengler T, Greco M, Quiñones S, Dulla CG, Raimondo JV, Figaji A, Hockman D. Steyn C, et al. bioRxiv [Preprint]. 2024 May 17:2023.09.29.560114. doi: 10.1101/2023.09.29.560114. bioRxiv. 2024. Update in: Nat Genet. 2024 Nov 20. doi: 10.1038/s41588-024-01990-6 PMID: 37808657 Free PMC article. Updated. Preprint.

References

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[1] Hodge, R. D. et al. Conserved cell types with divergent features in human versus mouse cortex. Nature 573, 61–68 (2019). - PubMed - PMC - DOI

[2] Hodge, R. D. et al. Conserved cell types with divergent features in human versus mouse cortex. Nature 573, 61–68 (2019). - PubMed - PMC - DOI

[3] Bakken, T. E. et al. Comparative cellular analysis of motor cortex in human, marmoset and mouse. Nature 598, 111–119 (2021). - PubMed - PMC - DOI

[4] Bakken, T. E. et al. Comparative cellular analysis of motor cortex in human, marmoset and mouse. Nature 598, 111–119 (2021). - PubMed - PMC - DOI

[5] Regev, A. et al. The Human Cell Atlas. eLife https://doi.org/10.7554/eLife.27041 (2017).

[6] Regev, A. et al. The Human Cell Atlas. eLife https://doi.org/10.7554/eLife.27041 (2017).

[7] Network, B. I. C. C. A multimodal cell census and atlas of the mammalian primary motor cortex. Nature 598, 86–102 (2021). - DOI

[8] Network, B. I. C. C. A multimodal cell census and atlas of the mammalian primary motor cortex. Nature 598, 86–102 (2021). - DOI

[9] Darmanis, S. et al. A survey of human brain transcriptome diversity at the single cell level. Proc. Natl Acad. Sci. USA 112, 7285–7290 (2015). - PubMed - PMC - DOI

[10] Darmanis, S. et al. A survey of human brain transcriptome diversity at the single cell level. Proc. Natl Acad. Sci. USA 112, 7285–7290 (2015). - PubMed - PMC - DOI

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A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

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A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

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Abstract

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Abstract

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