Cellular development and evolution of the mammalian cerebellum
Mari Sepp, Kevin Leiss, Florent Murat, Konstantin Okonechnikov, Piyush Joshi, Evgeny Leushkin, Lisa Spänig, Noe Mbengue, Céline Schneider, Julia Schmidt, Nils Trost, Maria Schauer, Philipp Khaitovich, Steven Lisgo, Miklós Palkovits, Peter Giere, Lena M. Kutscher, Simon Anders, Margarida Cardoso-Moreira, Ioannis Sarropoulos, Stefan M. Pfister, Henrik Kaessmann
Abstract
The expansion of the neocortex, a hallmark of mammalian evolution1,2, was accompanied by an increase in cerebellar neuron numbers3. However, little is known about the evolution of the cellular programmes underlying the development of the cerebellum in mammals. In this study we generated single-nucleus RNA-sequencing data for around 400,000 cells to trace the development of the cerebellum from early neurogenesis to adulthood in human, mouse and the marsupial opossum. We established a consensus classification of the cellular diversity in the developing mammalian cerebellum and validated it by spatial mapping in the fetal human cerebellum. Our cross-species analyses revealed largely conserved developmental dynamics of cell-type generation, except for Purkinje cells, for which we observed an expansion of early-born subtypes in the human lineage. Global transcriptome profiles, conserved cell-state markers and gene-expression trajectories across neuronal differentiation show that cerebellar cell-type-defining programmes have been overall preserved for at least 160 million years. However, we also identified many orthologous genes that gained or lost expression in cerebellar neural cell types in one of the species or evolved new expression trajectories during neuronal differentiation, indicating widespread gene repurposing at the cell-type level. In sum, our study unveils shared and lineage-specific gene-expression programmes governing the development of cerebellar cells and expands our understanding of mammalian brain evolution.
Datasets
1. snRNA-seq data for human cerebella from 9-12 developmental stages
Metadata
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glutamatergic_uncertain1107 cells isthmic_neuroblast265 cells Purkinje_defined35922 cells oligodendrocyte9431 cells interneuron_defined4559 cells GABA_DN_defined3613 cells Purkinje_maturing3153 cells interneuron_diff2246 cells VZ_neuroblast_32190 cells VZ_neuroblast_22035 cells glut_DN_defined1695 cells oligo_progenitor1633 cells glut_DN_maturing1044 cells NTZ_neuroblast_2644 cells NTZ_neuroblast_3356 cells NTZ_neuroblast_1281 cells isthmic_neuroblast265 cells Purkinje_defined_EB24656 cells Purkinje_defined_LB5829 cells progenitor_gliogenic5508 cells progenitor_VZ_early5495 cells GC_diff_2_early4962 cells progenitor_bipotent2898 cells progenitor_VZ_posterior1661 cells glut_DN_ventral1338 cells GC_diff_1_early1321 cells progenitor_isthmic884 cells progenitor_VZ_anterior739 cells progenitor_RL_early561 cells interneuron_early545 cells glut_DN_posterior357 cells progenitor_Nckap5_neg138 cells nonparenh_macrophage39 cells Purkinje_defined_EB24656 cells oligodendrocyte9431 cells Purkinje_defined_LB5829 cells progenitor_gliogenic5508 cells progenitor_VZ_early5495 cells Purkinje_defined5437 cells GC_diff_2_early4962 cells GABA_DN_defined3613 cells Purkinje_maturing3153 cells progenitor_bipotent2898 cells interneuron_diff2246 cells VZ_neuroblast_32190 cells VZ_neuroblast_22035 cells progenitor_VZ_posterior1661 cells glut_DN_ventral1338 cells GC_diff_1_early1321 cells glutamatergic_uncertain1107 cells glut_DN_maturing1044 cells progenitor_isthmic884 cells progenitor_VZ_anterior739 cells NTZ_neuroblast_2644 cells progenitor_RL_early561 cells interneuron_early545 cells glut_DN_posterior357 cells NTZ_neuroblast_3356 cells NTZ_neuroblast_1281 cells isthmic_neuroblast265 cells progenitor_Nckap5_neg138 cells nonparenh_macrophage39 cells HUM 11858 M Cr22617 cells HUM 13949 F Cr16683 cells HUM 2012258 F Cr7136 cells HUM #138 M CrDn6203 cells HUM 200978 M Cr25644 cells HUM #105 F CrCx5606 cells HUM #105 F CrVer5243 cells HUM 49910 Maryl_779 M Cr5046 cells HUM 49819 Maryl_121 M Cr4985 cells HUM #105 F CrFl4731 cells HUM #215 F CrDn4594 cells HUM 49844 Maryl_774 M Cr4462 cells HUM 2008267 F Cr4005 cells HUM 14278 M Cer3965 cells HUM #60 M CrVer3905 cells HUM 14471 F Cer3823 cells HUM 14409 M Cer3801 cells HUM 2012220 F Cr23181 cells HUM #138 M CrFl3156 cells HUM 14143 M Cer1732 cells 49910 Maryl_7795046 cells 49819 Maryl_1214985 cells 49844 Maryl_7744462 cells HsapDv:000002939300 cells HsapDv:000008216187 cells HsapDv:000013615580 cells HsapDv:000009714200 cells HsapDv:000004613847 cells HsapDv:000004813445 cells HsapDv:000005413197 cells HANCESTRO:056813602 cells NCBITaxon:9606180956 cells UBERON:0002037133741 cells UBERON:001464815580 cells UBERON:000213213953 cells adult (42 years)15580 cells adult (52 years)9359 cells toddler (2.8 years)8556 cells adult (46 years)8033 cells toddler (3.5 years)5644 cells newborn (5 days)5046 cells infant (7 months)4985 cells adult (44 years)4594 cells infant (9 months)4462 cells infant (6 months)3181 cells representative part58804 cells cerebellar granule cell66303 cells macroglial cell19623 cells oligodendrocyte9431 cells neuroblast (sensu Vertebrata)7232 cells unipolar brush cell3847 cells GABAergic neuron3828 cells glutamatergic neuron2739 cells cerebellar granule cell precursor2714 cells microglial cell1581 cells Bergmann glial cell1314 cells differentiation-committed oligodendrocyte precursor836 cells oligodendrocyte precursor cell697 cells immature astrocyte356 cells meningeal macrophage224 cells noradrenergic cell138 cells brain vascular cell79 cells central nervous system macrophage39 cells erythroid lineage cell38 cells acute myocardial infarction8033 cells congenital heart disease5046 cells hemisphere part of cerebellar posterior lobe15580 cells dentate nucleus13953 cells cerebellar cortex9649 cells cerebellum vermis lobule8033 cells African American13602 cells Carnegie stage 2239300 cells newborn human stage16187 cells 42-year-old human stage15580 cells 3-year-old human stage14200 cells 9th week post-fertilization human stage13847 cells 11th week post-fertilization human stage13445 cells 17th week post-fertilization human stage13197 cells 52-year-old human stage9359 cells 46-year-old human stage8033 cells 20th week post-fertilization human stage7849 cells Carnegie stage 186650 cells Carnegie stage 196087 cells 7-month-old human stage4985 cells 44-year-old human stage4594 cells 9-month-old human stage4462 cells 6-month-old human stage3181 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/72d37bc9-76cc-442d-9131-da0e273862db
Alias names
PMID38029793, PMC10808058
Cite this study
Sepp, M., Leiss, K., Murat, F., Okonechnikov, K., Joshi, P., Leushkin, E., Spänig, L., Mbengue, N., Schneider, C., Schmidt, J. and Trost, N., 2024. Cellular development and evolution of the mammalian cerebellum. Nature, 625(7996), pp.788-796. https://doi.org/10.1038/s41586-023-06884-x
