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

被引:1
|
作者
Steyn, Christina [1 ,2 ]
Mishi, Ruvimbo [1 ,2 ]
Fillmore, Stephanie [1 ,2 ]
Verhoog, Matthijs B. [1 ,2 ]
More, Jessica [1 ,2 ]
Rohlwink, Ursula K. [2 ,3 ]
Melvill, Roger [3 ]
Butler, James [2 ,4 ]
Enslin, Johannes M. N. [2 ,3 ]
Jacobs, Muazzam [2 ,5 ,6 ,7 ]
Sauka-Spengler, Tatjana [8 ,9 ]
Greco, Maria [10 ]
Quinones, Sadi [11 ,12 ]
Dulla, Chris G. [11 ]
Raimondo, Joseph V. [1 ,2 ,5 ]
Figaji, Anthony [2 ,3 ]
Hockman, Dorit [1 ,2 ]
机构
[1] Univ Cape Town, Dept Human Biol, Div Cell Biol, ZA-7925 Cape Town, South Africa
[2] Univ Cape Town, Neurosci Inst, Cape Town, South Africa
[3] Univ Cape Town, Dept Surg, Div Neurosurg, Cape Town, South Africa
[4] Univ Cape Town, Dept Med, Div Neurol, Cape Town, South Africa
[5] Univ Cape Town, Inst Infect Dis & Mol Med, Cape Town, South Africa
[6] Univ Cape Town, Dept Pathol, Div Immunol, Cape Town, South Africa
[7] Natl Hlth Lab Serv, Cape Town, South Africa
[8] Univ Oxford, MRC Weatherall Inst Mol Med, Radcliffe Dept Med, Oxford, England
[9] Stowers Inst Med Res, Kansas City, MO USA
[10] Univ Oxford, MRC Weatherall Inst Mol Med, Single Cell Facil, Oxford, England
[11] Tufts Univ, Grad Sch Biomed Sci, Sch Med, Dept Neurosci, Boston, MA USA
[12] Tufts Univ, Grad Sch Biomed Sci, Sch Med, Boston, MA USA
基金
新加坡国家研究基金会; 美国国家卫生研究院;
关键词
SYNAPTIC DENSITY; MUTATIONS CAUSE; TRANSCRIPTOME; PROTEIN; MALFORMATIONS; CHILDREN; NOTCH2; SOX11; AGE;
D O I
10.1038/s41588-024-01990-6
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.
引用
收藏
页码:2718 / 2730
页数:35
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