Spatial transcriptomics identifies L6 corticothalamic and L6b subplate-like heterotopic neurons in an epileptogenic SLC35A2-associated brain malformation.
- 1Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan
Abstract
Increased white matter (WM) heterotopic neurons are a pathological feature observed in various neurological and psychiatric disorders. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a drug-resistant epilepsy-associated cortical malformation characterized by increased WM heterotopic neurons and OLIG2-positive cells and frequently associated with somatic SLC35A2 mutations. However, the precise cellular identity of these heterotopic neurons remains unclear. Using imaging-based spatial transcriptomics (iST) of SLC35A2-mutated MOGHE tissues, we found that most WM heterotopic neurons exhibited molecular signatures of excitatory neurons. Further analyses revealed that these heterotopic excitatory neurons included prominent populations with layer 6 corticothalamic (CT)-like and layer 6b subplate neuron (SpN)-like molecular features. These findings were further supported by human immunohistochemistry and a Slc35a2 conditional knockout (cKO) mouse model. Together, our results provide a cellular characterization of WM heterotopic neurons in MOGHE and suggest a new perspective on disease pathophysiology centered on deep-layer excitatory neuronal populations.
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BibTeX
@misc{tabe2026spatial,
title = {{Spatial transcriptomics identifies L6 corticothalamic and L6b subplate-like heterotopic neurons in an epileptogenic SLC35A2-associated brain malformation.}},
author = {N. K. N. Tabe and S. Miyashita and K. Yagita and K. Iijima and K. Shimaoka and A. Hosaka and S. Okumiya and K. Nishitani and E. Usukura and K. Murayama and T. Sano and M. Takao and M. Iwasaki and M. Hoshino},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749069},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749069v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Spatial transcriptomics identifies L6 corticothalamic and L6b subplate-like heterotopic neurons in an epileptogenic SLC35A2-associated brain malformation.
AU - N. K. N. Tabe
AU - S. Miyashita
AU - K. Yagita
AU - K. Iijima
AU - K. Shimaoka
AU - A. Hosaka
AU - S. Okumiya
AU - K. Nishitani
AU - E. Usukura
AU - K. Murayama
AU - T. Sano
AU - M. Takao
AU - M. Iwasaki
AU - M. Hoshino
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749069
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749069v1
AB - Increased white matter (WM) heterotopic neurons are a pathological feature observed in various neurological and psychiatric disorders. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a drug-resistant epilepsy-associated cortical malformation characterized by increased WM heterotopic neurons and OLIG2-positive cells and frequently associated with somatic SLC35A2 mutations. However, the precise cellular identity of these heterotopic neurons remains unclear. Using imaging-based spatial transcriptomics (iST) of SLC35A2-mutated MOGHE tissues, we found that most WM heterotopic neurons exhibited molecular signatures of excitatory neurons. Further analyses revealed that these heterotopic excitatory neurons included prominent populations with layer 6 corticothalamic (CT)-like and layer 6b subplate neuron (SpN)-like molecular features. These findings were further supported by human immunohistochemistry and a Slc35a2 conditional knockout (cKO) mouse model. Together, our results provide a cellular characterization of WM heterotopic neurons in MOGHE and suggest a new perspective on disease pathophysiology centered on deep-layer excitatory neuronal populations.
ER -