Supplementary Table 4 from Schmitz et al. Nature. 2022. - Dictionary of initial and terminal classes. Qualitative definitions of classes explored in the atlas with extended explanations for inferences about initial–terminal class relationships.
| Class Name | Class Category | Description | Aliases or Subclasses | Derived From | Derived From Explanation |
|---|---|---|---|---|---|
| CGE_NR2F2/PROX1 | initial | Newborn neurons from the caudal ganglionic eminence | |||
| LGE-OB_MEIS2/PAX6 | initial | Newborn neurons of the LGE_MEIS2/PAX6 class which are found in the adult olfactory bulb | GC-2 (doi: 10.1016/j.celrep.2018.11.034) | ||
| LGE_FOXP1/ISL1 | initial | Newborn neurons of the inner LGE which are FOXP1/ISL1 positive | |||
| LGE_FOXP1/ISL1/NPY1R | initial | A ventral subclass of LGE_FOXP1/ISL1, which is EBF1 negative and NPY1R positive, and is apparently distinct early in differentiation | |||
| LGE_FOXP1/PENK | initial | Newborn neurons of the inner LGE which are FOXP1/PENK positive | |||
| LGE_FOXP2/TSHZ1 | initial | Newborn neurons from the external/dorsal LGE which are FOXP2/TSHZ1 positive and FOXP1/NPY negative. We observe in immunos and transcriptome trajectories they are likely SP8 and SCGN positive until they become strongly FOXP2 positive, at which point those genes become undetectable. | |||
| LGE_MEIS2/PAX6 | initial | Newborn neurons of the external/dorsal LGE which are MEIS2/PAX6/TSHZ1/SCGN(macaque only)/ETV1/FOXP2(but barely detectable with immunofluorescence) positive and FOXP1/NR2F2 negative | |||
| LGE_MEIS2/PAX6/SCGN | initial | A subclass of LGE_MEIS2/PAX6 which is also positive for CALB2, ZIC1 and SCGN in the mouse, and is apparently distinct early in differention. | |||
| MGE_CRABP1/MAF | initial | Newborn neurons of the MGE which are CRABP1/MAF/NKX2-1/ETV1/LHX6 positive and are seen migrating through the MGE and striatum by RNAscope. | |||
| MGE_CRABP1/TAC3 | initial | A sister initial class to MGE_CRABP1/MAF. Appears by RNAscope to become LHX8+/- only after reaching striatal destinations. Adult terminal classes covered by Krienen et al. (doi: 10.1038/s41586-020-2781-z) | |||
| MGE_LHX6/MAF | initial | Newborn neurons from the MGE which are positive for NKX-1/LHX6/MAF/MAFB/ERBB4/SST | |||
| MGE_LHX6/NPY | initial | Newborn neurons from the MGE which may be postmitotic derivatives from MGE_LHX6/MAF, but appear to distribute to the basal nuclei as well as the cortex. Expresses LHX6/MAF/NPY/CORT/CHODL. See Ctx/BN_SST/CHODL. | |||
| RMTW_ZIC1/RELN | initial | Newborn Cajal-Retzius neurons found in cortical layer 1 and derived from the Rostro-medial telencephalic wall (RMTW). Highly expresses RELN. Appear to be glutamatergic, but express low levels of GAD genes. Reported to mostly disappear before maturity, and no corresponding terminal class is observed in adult. | Cajal-Retzius Cells, Horizontal Cells of Cajal | ||
| VMF_CRABP1/LHX8 | initial | These cells may arise from the MGE-like GBX1+ portion of the septum. | |||
| VMF_LHX1/POU6F2 | initial | POH or POA-derived neurons expressing PAX6/NR2F2/ISL1/SP8/MEIS2/LHX1/TSHZ2, reported to become TH+/SCGN+/- hypothalamic dopaminergic cells | may contribute to dopaminergic groups A11-15 (doi: 10.1038/s41467-020-18231-z / doi:10.1016/j.tins.2007.03.006) | ||
| VMF_NR2F2/LHX6 | initial | Neurons with a VMF expression profile that are NR2F2/LHX6/CALB1 positive. Found in mouse MGE, CGE and cortex dissections with unknown derivative adult profile. This is a possible source of POA derived cortical interneurons (doi: 10.7554/eLife.32017 , doi: 10.1523/JNEUROSCI.4068-11.2011) | |||
| VMF_PEG10/DLK1 | initial | POH or POA-derived newborn neurons that express PEG10/DLK1/HMX3/HAP1/TSHZ2/NR2F2. These cells are reported to cross the telencephalon-diencephalon boundary and to populate the amygdala. (doi: 10.1038/nn.2556) | |||
| VMF_TMEM163/OTP | initial | Hypothalamus-derived newborn neurons that express VMF_TMEM163/OTP. These cells appear to be excitatory, their top marker is SLC17A6. Thus they are not included in our taxonomy, nor does their derivative terminal class(es) appear to make thresholds to be included in the dataset. | |||
| VMF_ZIC1/ZIC2 | initial | Septum-derived newborn neurons expressing ZIC1/2/3/4. Adult septum is undersampled in both macaque and mouse, and so derivative terminal class may be missing from dataset. | |||
| Amy/Hypo_HAP1/PEG10 | terminal | These cells were found in both hypothalamus and amygdala mouse samples. They appear to be the neurons which are reported to cross the telencephalon-diencephalon boundary and to populate the amygdala (doi: 10.1038/nn.2556). Interestingly their expression suggests they use both GABA and Glutamate neurotransmitters. | VMF_PEG10/DLK1 or VMF_TMEM163/OTP | ||
| BN-eSPN_FOXP2/TSHZ1 | terminal | This terminal class appears to consist of two related classes which coclustered in our leiden clustering. In the striatum cells express CASZ1/OTOF and are known as eccentric spiny neurons (eSPNs). The other clear subclass is derived from amygdala samples, where these cells are known as intercalated cells (ITCs). In both locations they express FOXP2/4 but do not express FOXP1 | eccentric spiny neurons, intercalated cells of the amygdala, D1H(doi:10.1016/j.neuron.2019.11.004), PCDH8+ SPNs(doi:10.1016/j.celrep.2016.06.059) | LGE_FOXP2/TSHZ1 | We believe the preponderance of the evidence points to LGE_FOXP2/TSHZ1 being the precursor of BN-eSPN_FOXP2/TSHZ1. This is supported by the RNA velocity absorption analysis, the more perfect matching of markers like OPRM1, CASZ1 and lack of FOXP1 in macaque and mouse, expression of CASZ1 in the dorsal/external LGE where SCGN/FOXP2 are also seen (histology), trajectory expression showing that immature cells of FOXP2/TSHZ1 expressing SCGN, SP8 and ETV1. LGE_FOXP1/ISL1 is also a possible source but we believe the partial transcriptomic correspondence between LGE_FOXP1/ISL1 and BN-eSPN_FOXP2/TSHZ1 is spuriously driven by activation of shared projection markers and DRD1 as these neurons mature. |
| Ctx/BN_SST/CHODL | terminal | This terminal class is distributed to the cortex and also the basal nuclei. In the cortex these neurons are well known for high expression of SST and CHODL. They also likely correspond to hippocampal SST/NPY/NOS1+ ivy and neurogliaform (NGF) cells (doi:10.1523/JNEUROSCI.5123-09.2010 ). | cortical long-projecting SST+ neurons, hippocampal ivy and NGF cells, striatal plateau low-threshold-spiking neurons | MGE_LHX6/NPY | |
| Ctx_CCK/DPY19L1 | terminal | Rare class of cortical interneurons | CGE_NR2F2/PROX1 | ||
| Ctx_CCK/VIP | terminal | Common CCK+ VIP+/- class of CGE-derived cortical interneurons | CCK basket cells, VIP bipolar cells | CGE_NR2F2/PROX1 | |
| Ctx_LAMP5/NDNF | terminal | Class of cortical/hippocampal formation interneurons | Adarb2/Ndnf-HPF cells in Allen taxonomy. | CGE_NR2F2/PROX1 | |
| Ctx_LHX6/LAMP5 | terminal | LHX6/LAMP5+ class of cortical chandelier interneurons | CHC2 Cortical Chandelier Cells (doi:10.1038/s41586-018-0654-5) | MGE_LHX6/MAF | This class is reported to be derived from NKX2-1+ cells using Cre-Lox lineage tracing(doi:10.1016/j.cell.2017.08.032, Paul et al). We find that the most parsimonious explanation is that these are MGE derived interneurons which bear transcriptomic similarity to CGE-derived LAMP5 cells due to very high expression of LAMP5. |
| Ctx_LHX6/PVALB | terminal | Common PVALB+ MGE-derived cortical interneurons | PVALB basket cells, fast spiking interneurons | MGE_LHX6/MAF | |
| Ctx_LHX6/SST | terminal | Common SST+ MGE-derived cortical interneurons | Martinotti SST+ interneurons | MGE_LHX6/MAF | |
| Ctx_NR2F2/PAX6 | terminal | Rare class of cortical interneurons. | Adarb2/Pax6 cells in Allen taxonomy. | CGE_NR2F2/PROX1 or VMF classes or (unlikely) LGE_MEIS2/PAX6 | Terminal class doesn't express MEIS2/FOXP2/STXBP6/ETV1 or any other markers which would be expected from LGE derived cells but expresses CGE/VMF marker NR2F2, and RNA velocity suggests CGE_NR2F2/PROX1 is more likely as origin. |
| Ctx_PROX1/LAMP5 | terminal | Common LAMP5+ class of CGE-derived cortical interneurons | Lamp5 interneurons | CGE_NR2F2/PROX1 | |
| Ctx_PROX1/SNCG | terminal | Common SNCG+ class of CGE-derived cortical interneurons | Sncg interneurons | CGE_NR2F2/PROX1 | |
| Ctx_PVALB/VIPR2 | terminal | PVALB/VIPR2+ class of cortical chandelier interneurons. | CHC1 Cortical Chandelier Cells (doi:10.1038/s41586-018-0654-5) | MGE_CRABP1/MAF or MGE_LHX6/MAF | RNA velocity analysis is unclear as to which MGE class is the more likely precursor initial class. Cortical PVALB cells are assumed to descend from MGE_LHX6/MAF class, while striatal PVALB cells descend from MGE_CRABP1/MAF, (doi: 10.1016/j.celrep.2018.07.053), but the Ctx_PVALB/VIPR2 class is distinct from the Ctx_LHX6/PVALB class and shows transcriptional similarities to both candidate initial classes, for instance sharing PTHLH and continuing adult NKX2-1 expression with MGE_CRABP1/MAF. |
| Ctx_SST/NDNF | terminal | SST/NDNF+ class of cortical interneurons | MGE_LHX6/MAF | ||
| GP_GBX1/GABRA1 | terminal | GBX1/GABRA1/PVALB/ZIC1 neurons which appear to make up a large percentage of the neurons in the globus pallidus | fast-spiking “prototypical” globus pallidus neurons (doi: 10.1016/j.cell.2018.07.028) | VMF_CRABP1/LHX8 | |
| OB-GC NR2F2/PENK | terminal | A class of granule cells of the olfactory bulb | GC-6 (doi: 10.1016/j.celrep.2018.11.034) | LGE_MEIS2/PAX6 (LGE-OB_MEIS2/PAX6) | |
| OB-GC_RPRM | terminal | A rare class of granule cells of the olfactory bulb | GC-3 (doi: 10.1016/j.celrep.2018.11.034) | LGE_MEIS2/PAX6 or LGE_FOXP2/TSHZ1 | |
| OB-GC_STXBP6/PENK | terminal | The most prominent class of granule cells of the olfactory bulb | GC-5 (doi: 10.1016/j.celrep.2018.11.034) | LGE_MEIS2/PAX6 (LGE-OB_MEIS2/PAX6) | |
| OB-PGC_FOXP2/CALB1 | terminal | FOXP2/CALB1 positive periglomerular cells (PGC) of the olfactory bulb | PGC-3 (doi: 10.1016/j.celrep.2018.11.034), calbindin+ PGC | LGE_FOXP2/TSHZ1 | |
| OB-PGC_TH/SCGN | terminal | MEIS2/PAX6/ETV1/TH/SCGN positive periglomerular cells of the olfactory bulb and accessory olfactory bulb | PGC-2 (doi: 10.1016/j.celrep.2018.11.034), dopaminergic group A16 (doi: 10.1016/S0165-0173(00)00034-5 / doi.org/10.1016/j.tins.2007.03.006 short axon dopaminergic cells, THLI striatum cells | LGE_MEIS2/PAX6/SCGN or LGE_MEIS2/PAX6 | We believe that TH/SCGN+ PSCs are derived from this group rather than the hypothalamic VMF_LHX1/POU6F2 as PSCs are negative for NR2F2, in addition to their location far removed from the telencephalon-diencephalon boundary. |
| OB-PGC_ZIC | terminal | CALB2/SP8/ETV1/ZIC1/2/4 positive periglomerular cells of the olfactory bulb | PGC-1 (doi: 10.1016/j.celrep.2018.11.034) | LGE_MEIS2/PAX6 or septum | |
| Str-IN_CRABP1/MAF | terminal | Striatal GABAergic interneurons CRABP1/ETV1/NKX2-1/KIT/MAF+ in adult rodent and primates. | TH+ (MGE-derived) striatal interneurons, PVALB+ (MGE-derived) striatal interneurons, PTHLH+ (MGE-derived) striatal interneurons | MGE_CRABP1/MAF | |
| Str-IN_CRABP1/TAC3 | terminal | Striatal GABAergic interneurons CRABP1/ETV1/NKX2-1/MAF/TAC3/STXBP6+ in adult primates but not rodents, nor laurasiatherians. | TAC3+ (MGE-derived) striatal interneurons | MGE_CRABP1/TAC3 | |
| Str-dSPN_FOXP1/ISL1 | terminal | Direct (striatonigral projecting) spiny projection neurons (DRD1+) of the basal nuclei. Subclasses include orthogonal axes of variation which appear to be overlaid later in development such as dorsoventral and patch-matrix gene expression identities, perhaps due to striosome cells appearing to be born before matrix cells in mouse (doi:10.1016/j.neuron.2018.06.021.) | dSPN, direct medium spiny neuron | LGE_FOXP1/ISL1 | |
| Str-iSPN_FOXP1/PENK | terminal | Indirect (striatopallidal projecting) spiny projection neurons (DRD2+) of the basal nuclei. Subclasses include orthogonal axes of variation which appear to be overlaid later in development such as dorsoventral and patch-matrix gene expression identities. | iSPN, indirect medium spiny neuron | LGE_FOXP1/PENK | |
| Str_LHX8/CHAT | terminal | Cholinergic cells of the basal nuclei and septum which express ZIC1/CHAT/LHX8 and choline transporters | cholinergic striatal interneurons, septohippocampal cholinergic pathway cells | VMF_CRABP1/LHX8 | |
| DWMIN_NR2F2/SP8 | terminal | The terminal class identity and transcriptome is unknown. We observed many cells matching these markers in the deep white matter at late developmental and mature ages in the macaque, but can't speculate about them beyond noting their existence in large numbers. | CGE_NR2F2/PROX1 (Presumed), VMF also possible | Presumed to be CGE derived, but could also be POA/POH derived given the small number of markers observed in immunostaining | |
| DWMIN_MEIS2/PAX6 | terminal | The terminal class full transcriptome is unknown. Deep white matter inhibitory neurons (DWMIN) derived from the arc and arc-ACC migratory streams. They appear to express MEIS2/PAX6/SP8/SCGN and low/no FOXP2, TH or NR2F2 protein. | Possible component of Allen cortical Meis2 | LGE_MEIS2/PAX6 | While it was unclear whether mature cortical DWMIN_MEIS2/PAX6 cells in the adult mouse clustered with olfactory bulb or were hidden amongst another larger terminal class, Figure 4 and ED provides evidence that neurons of class migrate into and remain in the deep white matter. |
| SWMIN_FOXP2/FOXP4 | terminal | The terminal class full transcriptome is unknown. Superficial white matter inhibitory neurons (SWMIN), which appear to derive from a medial migratory stream from the LMS which continues into VMPFC. Their existence is largely based upon LGE_FOXP2/TSHZ1 cells found in cortical developing macaque samples, and FOXP2/SP8 or FOXP2/DLX2 stains in macaque superficial white matter. These cells appeared very rare in histology. | Likely component of Allen cortical Meis2 | LGE_FOXP2/TSHZ1 | Macaque transcriptome and histology suggests these cells still express some SP8 and SCGN while migrating. These cells did not cluster distinctly in mouse adult data. |
| Str-SLN_TH/SCGN | terminal | The terminal class full transcriptome is unknown. These striatum laureatum neurons wreaTHe the boundaries of the striatum (especially externally), including the claustrum. These cells share many markers with OB-PGC_TH/SCGN, however this requires further transcriptomic characterization. These cells express MEIS2/PAX6/SP8/TH/SCGN but do not appear to express FOXP2 (SPN), NKX2-1 (MGE-derived striatal interneuron) or NR2F2 (CGE or POA/POH-derived). It appears that most studies of TH+ cells of the striatum don't distinguish between Str-SLN_TH/SCGN and Str-IN_CRABP1/MAF/TH. Informally called wreaTH cells. | LGE_MEIS2/PAX6/SCGN or LGE_MEIS2/PAX6 (presumed) | ||
| G1-phase_SLC1A3/ATP1A1 | technical | Cells in G1-phase of cell cycle | |||
| S-phase_MCM4/H43C | technical | Cells in S-phase of cell cycle | |||
| G2-M_UBE2C/ASPM | technical | Cells in G2/M phase of cell cycle | |||
| Transition | technical | Cells of multiple classes which aren't well distinguished by leiden clustering due to cell cycle and early maturation variation. Excluded from most analyses to avoid cross contamination of initial classes | |||
| Glia | technical | Diverse glial cells which pass filters to be part of the dataset but are not analyzed here. | |||
| Excitatory | technical | Excitatory cells which pass filters to be part of the dataset. Expresses SLC17A6/7 and tiny amount of GAD or DLX genes, so are not analyzed |