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Record W4415763225 · doi:10.1101/2025.10.31.685953

A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences

2025· preprint· en· W4415763225 on OpenAlexaff
Olivia Davis, Seph M. Palomino, Satoshi Ishishita, Helen Poldsam, Jane Brandon, Nikhil Nageshwar Inturi, Hemanth Mydugolam, Ibrahim Khan, Nethra Selvakumaran, Stephanie Shiers, Muhammad Saad Yousuf, Erin Vines, Peter Horton, Tariq Khan, Anna Cervantes, Jeffrey C. Reese, Amol Patwardhan, Gregory Dussor, Eric Meyers, Diana Tavares‐Ferreira, Allan‐Hermann Pool, Theodore J. Price

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsMcGill University
FundersUniversity of Texas at Dallas
KeywordsSpinal cordLumbar Spinal CordSexual dimorphismDorsumNeuroanatomyCentral nervous systemSensory systemCell type

Abstract

fetched live from OpenAlex

The spinal cord is the gateway for sensory information from the body as it ascends to the brain, as well as a major motor output center of the nervous system. It is also a key location for sensory-motor integration, and a processing site for nociceptive information that eventually drives pain perception in the brain. Tremendous progress has been made in understanding spinal cord circuits using genetic and single cell sequencing approaches in mice. Recently, several groups have conducted single-nucleus and spatial sequencing studies in postmortem human spinal cord tissue. However, the spatial properties of spinal cord cellular diversity and potential sex differences that might be important for human physiology remain unexplored. We conducted deep single-nucleus sequencing on dissected lumbar dorsal and ventral spinal cord samples from 11 organ donors, including 6 females and 5 males, and anatomically annotated spinal cord cell types with 10X Xenium single-molecule spatial transcriptomics. We identified 34 spatially and genetically defined neuron classes, many of which have clearly recognizable conserved orthologs in the rodent spinal cord. We also identified sex specific cell types and states within multiple glial types, but not neurons, demonstrating sexual dimorphism at the transcriptomic cell-type level in the adult human spinal cord. The spatial and single-nucleus atlas resulting from our work build upon previous knowledge to better understand human spinal cord physiology and to identify drug targets for neurological diseases affecting the spinal cord, in particular pain.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.142
Threshold uncertainty score0.898

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.214
Teacher spread0.202 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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