Why Mammals Anchor the Derived End
The BrainStorm sampling is deliberately skewed toward non-mammalian lineages, yet mammals occupy the derived pole of the atlas: the branch where ancestral glial and neuronal programs reach their greatest molecular complexity. Four mammals were newly profiled in this study (chinchilla, green monkey, ferret and baboon), and they join 34 species drawn from public datasets, from the marsupial opossum to humans. Together these 38 species contribute 184,583 cells to the 492,121-cell analysis layer and define the reference against which lineage-specific innovations are measured.
Four Newly Profiled Mammals
Chinchilla, green monkey, ferret and baboon were newly profiled for this atlas, adding fresh single-nucleus resources on glires and primates to the public mammalian backbone.
34 Public Datasets
The public wing spans rodents, lagomorphs, bats, carnivores, ungulates, cetaceans, marsupials and a broad primate sampling from mouse lemurs to the great apes.
184,583 Mammal Cells
Mammals contribute 184,583 cells to the 492,121-cell analysis layer, the largest tetrapod block and the sampling backbone for the derived end of the vertebrate brain.
Mammal-Restricted Astrocyte Clusters: NFIA and SOX9
Astrocytes co-evolve with neurons, and across the five major vertebrate lineages they resolve into a conserved yet progressively diversified set of subpopulations. Mammals stand out for the most divergent astrocyte regulatory programs: mammal-restricted subclusters show the highest regulatory divergence in the atlas, marked by strong induction of NFIA and SOX9, transcription factors associated with mature astrocyte differentiation, metabolic support and synaptic modulation.
NFIA and SOX9 Induction
Mammal-restricted astrocyte subclusters carry strong NFIA and SOX9 signatures, linking mature astrocyte identity to metabolic support and synaptic modulation in the large mammalian brain.
ZHX3 and ETV1 States
Among the resolution-0.5 astrocyte subclusters, Ast_00_ZHX3 reaches a cell fraction of 99.6% in mammals, while Ast_08_ETV1 is enriched 1.88x in mammals, consistent with amplification of specialized astrocyte states.
NFIB Co-Expression
NFIB is co-upregulated with NFIA in a mammal-enriched astrocyte cluster (cluster c4; z = 1.77 and z = 2.95 respectively), pairing two NF transcription factors in the mature mammalian program.
A Mammalian-Specific Precursor State: OPC_14_ETV1
The atlas resolves 16 oligodendrocyte precursor cell (OPC) subclusters and 11 oligodendrocyte subclusters, a modular regulatory architecture in which transcription factors such as RFX3, MAFK and MITF are reused across phylogeny. Mammals add a distinctive state: the mammalian-specific enrichment of OPC_14_ETV1 points to a recent innovation, potentially fine-tuning myelination for the complex, large-brained mammals.
OPC_14_ETV1, Mammalian-Specific
OPC_14_ETV1 is specifically enriched in mammals, a state interpreted as a recent innovation that may fine-tune myelination for large, complex mammalian brains.
Ancient Genes, New Tricks
The mammalian OPC state is built by co-opting an ancestral gene regulatory network rather than by wholesale gene birth, illustrating how regulatory recombination generates lineage diversity from deeply conserved components.
16 OPC, 11 Olg Subclusters
Across the whole atlas, the oligodendroglial lineage resolves into 16 OPC and 11 mature oligodendrocyte subclusters on a deeply conserved OPC-to-oligodendrocyte axis that runs from teleost fishes to mammals.
A Derived Microglial State Dominates the Mammalian Brain
Microglial diversity resolves into an ancient layer conserved across jawed vertebrates and a derived, amniote-enriched module. In mammals the derived state Mic_011 takes over: it accounts for a median of approximately 94% of mammalian microglia and is significantly enriched in mammals at the species level. This shifts the mammalian microglial population from ancestral toward derived configurations.
Mic_011
Mic_011 is enriched in mammals with a species-level median of 94% of microglia, at a false discovery rate of 1.6e-12.
MEF2A · ARC · PPARGC1A
The derived cluster acquires regulators of neuroinflammation (MEF2A), synaptic plasticity (ARC) and metabolic adaptation (PPARGC1A), aligning microglial state with mammalian neural circuit demands.
From Ancestral to Derived
Whereas fishes are dominated by ancestral microglial states (Mic_005, FDR 3.8e-14), mammals show a consistent shift toward derived states such as Mic_011, a composition shift anchored at deep phylogenetic branches.
Cortical Layer V Identity Within the Mammalian Range
A prior cross-species study of primary motor cortex (M1) reported that the proportions of layer V intratelencephalic (L5 IT), extratelencephalic (L5 ET) and layer 5/6 near-projecting (L5/6 NP) neurons are consistently reduced in the human lineage. The BrainStorm atlas provides an independent view across 35 mammalian species: the percentages of human excitatory neurons with high L5_IT, L5_ET and L5/6_NP signature scores fall within the mid-to-upper range of other mammals, at the 49th to 80th percentile. This comparison is descriptive.
Human Within the Mammalian Range
Across 35 mammalian species, human excitatory neurons with high layer V signature scores sit at the 49th to 80th percentile of mammals, within the mid-to-upper range and showing no consistent reduction.
Not Directly Comparable
The human and mouse libraries here sample whole brains or large regions rather than dissected M1, so the two studies are not directly comparable; the discrepancy may reflect sampling scope.
L5/6 NP Is Two Genes
The L5/6_NP signature comprises only two genes (ETV1 and NPNT) and is treated as exploratory; a strong statement on human-specific layer V proportion shifts is withheld at the current resolution.
All 38 Mammal Species
Four mammal species in this atlas were newly profiled; 34 were drawn from existing public datasets. The list below follows the classification in the species library table.
Newly Sequenced · 4 Species
| Common Name | Latin Name |
|---|---|
| Chinchilla | Chinchilla lanigera |
| Green monkey | Chlorocebus sabaeus |
| Ferret | Mustela putorius furo |
| Baboon | Papio anubis |
Public Datasets · 34 Species
| Common Name | Latin Name |
|---|---|
| Arctic ground squirrel | Urocitellus parryii |
| Beagle dog | Canis lupus familiaris |
| Blind mole rat | Nannospalax galili |
| Bonobo | Pan paniscus |
| Chimpanzee | Pan troglodytes |
| Chinese rufous horseshoe bat | Rhinolophus sinicus |
| Coyote | Canis latrans |
| Crab-eating macaque | Macaca fascicularis |
| Domestic cat | Felis catus |
| Domestic pig | Sus scrofa |
| Gorilla | Gorilla gorilla |
| Greater short-nosed fruit bat | Cynopterus sphinx |
| Guinea pig | Cavia porcellus |
| Hamster | Mesocricetus auratus |
| Human | Homo sapiens |
| Leschenault's rousette | Rousettus leschenaultii |
| Marmoset | Callithrix jacchus |
| Mouse | Mus musculus |
| Mouse lemur | Microcebus murinus |
| Nine-banded armadillo | Dasypus novemcinctus |
| Opossum | Monodelphis domestica |
| Owl monkey or Ma's night monkey | Aotus nancymaae |
| Peromyscus maniculatus | Peromyscus maniculatus |
| Peromyscus polionotus | Peromyscus polionotus |
| Pig-tailed macaque | Macaca nemestrina |
| Rabbit | Oryctolagus cuniculus |
| Rat | Rattus norvegicus |
| Rhesus macaque | Macaca mulatta |
| Rickett's big-footed bat | Myotis ricketti |
| Sheep | Ovis aries |
| Short-finned pilot whale | Globicephala macrorhynchus |
| Small-eared galago | Otolemur garnettii |
| Squirrel monkey | Saimiri sciureus |
| Tree shrew | Tupaia belangeri |
Dive Deeper
All 100 Vertebrates
Browse the complete species catalog across all lineages.
Fishes
Contrast the mammalian derived end with the basal fish backbone.
Astrocytes
NFIA and SOX9 cladogenesis in the glial lineage.
Microglia
The derived Mic_011 state in the mammalian brain.