Niacin promotes motor function recovery after spinal cord injury via Hcar2-dependent microglia immunometabolic regulation.

Code ↔ Paper

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The 4 matches

[1] § MATERIALS AND METHODS › Bioinformatic analysis of publicly available single‐cell RNA sequencing datasets ↔ vignettes/mixscape_vignette.Rmd, lines 78–133 · score 0.81 · uniform manifold approximation, principal component, dimensionality reduction, UMAP, biological, Gene expression
[2] § MATERIALS AND METHODS › Bioinformatic analysis of publicly available single‐cell RNA sequencing datasets ↔ R/differential_expression.R, lines 455–538 · score 0.80 · Wilcoxon rank sum, DESeq2, scRNA, Linear, single cell, predicted
[3] § MATERIALS AND METHODS › Statistical analysis ↔ R/preprocessing.R, lines 4370–4415 · score 0.56 · statistical power, standard deviation, variance, score
[4] § MATERIALS AND METHODS › Bulk RNA sequencing and analysis ↔ R/generics.R, lines 109–170 · score 0.56 · DESeq2, quality controlled, genome, Gene expression, transcripts, RNA

Paper

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The authors' code

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Overview

Authors: Hua Du¹, Lingnian Zeng¹, Chan Liu¹, Huyao Zhou¹, Xia Wang¹, Qing Ai¹, Jinpiao Zhu², Nong Xiao¹

Institutions: Children's Hospital of Chongqing Medical University (China); Chongqing Medical University (China); Children's Hospital of Zhejiang University (China); Zhejiang University (China)

Journal: Clinical and translational medicine, volume 16, issue 5, article e70683

Dates: received 17 January 2026; accepted 23 April 2026; published online 1 May 2026; in print May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1002/ctm2.70683 · PMID 42068080 · PMCID PMC13135113 · OpenAlex W7159770380

Open access: gold, a free copy (OpenAlex)

Status: code verified

Categories: genetics / omics (modality), mouse (organism), non-human primate (organism), other condition (population), cellular / molecular (subfield)

Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions

Keywords: hydroxycarboxylic acid receptor 2, immunometabolism, metabolic reprogramming, microglia, neuroinflammation, niacin, spinal cord injury

MeSH: Microglia*, Niacin*, Receptors, G-Protein-Coupled*, Recovery of Function*, Spinal Cord Injuries*, Animals, Disease Models, Animal, Mice (* major topic)

Topic: Spinal Cord Injury Research (Pathology and Forensic Medicine, Medicine), according to OpenAlex

Funding: Children's Hospital of Chongqing Medical University of Medicine Pre-Research Fund (29701259); "Pioneer" and "Leading Goose" R&D Program of Zhejiang (2025C02082); Children's Hospital of Zhejiang University School of Medicine Pre-Research Fund (CHZJU2023YY006); National Natural Science Foundation of China (82401498); Key Project of Medical and Health Science and Technology Plan of Zhejiang Province (WKJ-ZJ-2536); Special Fund for the Incubation of Young Clinical Scientist, the Children's Hospital of Zhejiang University School of Medicine (CHZJU2024YS001)

Citations: not cited yet (Europe PMC); 50 references in the paper

Abstract

Background: Traumatic spinal cord injury (SCI) induces a robust local inflammatory response that can both facilitate repair and exacerbate pathology. Hydroxycarboxylic acid receptor 2 (Hcar2) is known to exert immunomodulatory effects; however, its role in SCI and its potential for targeting Hcar2 to alleviate motor deficits remain unclear.

Methods: The spinal cord transcriptome following SCI, with a focus on Hcar2, was analysed via publicly available single‐cell RNA sequencing datasets from mice and rhesus macaques. Additionally, an in vivo SCI mouse model with Hcar2 knockout and an in vitro LPS‐induced BV2 microglial model were established to assess Hcar2 gene and protein expression, microglial activation and inflammatory responses via bulk RNA sequencing, immunofluorescence staining, Western blotting, and real‐time polymerase chain reaction. To evaluate the protective effects of Hcar2 activation, niacin, a known Hcar2 agonist, was administered to mice or BV2 cells, followed by assessments of the inflammatory response and motor function.

Results: Hcar2 gene expression, which was enriched predominantly in spinal cord microglia, was upregulated following SCl, peaking at 7 days post‐SCl. Genetic knockout of Hcar2 decreased the percentage of impaired anti‐inflammatory polarized microglia and increased the inflammatory response. In contrast, Hcar2 activation with niacin in LPS‐stimulated microglia BV cell models reversed mitochondrial dysfunction, increased the oxygen consumption rate and reduced the expression of the cytokines IL‐6 and IL‐1β. The administration of niacin to SCl mice upregulated anti‐inflammatory microglia, reduced the expression of multiple proinflammatory cytokines, increased the number of motor neurons and improved motor function recovery. Notably, all these protective effects were abolished by genetic loss of Hcar2.

Conclusions: Hcar2 serves as a critical regulator of microglial polarization, promoting the switch from a proinflammatory phenotype to an anti‐inflammatory phenotype through immunometabolic reprogramming. Targeting Hcar2 with niacin may offer a translatable therapeutic strategy to improve functional recovery after SCl.

Key Points: Hcar2 is identified as a conserved, injury‐induced metabolic checkpoint specifically enriched in microglia following spinal cord injury.

Hcar2 activation reprogrammes microglial metabolism from glycolysis to oxidative phosphorylation to drive reparative anti‐inflammatory polarization.

Pharmacological targeting of Hcar2 with niacin resolves neuroinflammation and promotes functional motor recovery in an Hcar2‐dependent manner.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above, with 4 matches between paragraphs and lines of code.

satijalab/seurat

License: other

State: the link answers, verified on 27 September 2026

Evidence: files inventoried

Commit: 586015abde10618ecb32d3fe632267a83317a08d, 21 September 2026

Languages: R (114), C++ (8), C/C++ (4), C (1)

Size: 455 files, 127 scripts

Software Heritage: archived

Found in: “Bioinformatic analysis of publicly available sin”

Holds: README, license file, environment (DESCRIPTION), tests, continuous integration, documentation, 70 notebooks

Not found: CITATION.cff

Tools: Seurat (75 files), ggplot2 (48 files), patchwork (27 files), tidyverse (19 files), cowplot (10 files), reshape2 (3 files), SingleCellExperiment (3 files), Plotly (2 files), data.table (1 file), DESeq2 (1 file), Harmony (1 file), igraph (1 file), limma (1 file), Monocle 3 (1 file), reticulate (1 file), UMAP (1 file)

Availability: 1 check, the latest on 27 September 2026: the link answers

27 September 2026: the link answers

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At the source: github.com/satijalab/seurat

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Data

Datasets cited

geo:GSE162610 — at NCBI GEO; found in “Bioinformatic analysis of publicly available…”

Data availability statement

The datasets generated and analysed during the current study are available from the corresponding author upon reasonable request. The RNA‐seq data have been deposited in the NCBI Sequence Read Archive (SRA) under accession number PRJNA1441145. Publicly available single‐cell RNA sequencing data used in this study were obtained from the Gene Expression Omnibus (GEO) under accession number GSE162610 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162610), GSE196929 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196929) and GSE228032 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228032).

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Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 7 keywords, 8 MeSH terms, 6 funders, 50 references.

Cite

This paper

Du, H., Zeng, L., Liu, C., Zhou, H., Wang, X., Ai, Q., Zhu, J., & Xiao, N. (2026). Niacin promotes motor function recovery after spinal cord injury via Hcar2-dependent microglia immunometabolic regulation. Clinical and translational medicine, 16(5), e70683. https://doi.org/10.1002/ctm2.70683

BibTeX

@article{du2026niacin, author = {Du, Hua and Zeng, Lingnian and Liu, Chan and Zhou, Huyao and Wang, Xia and Ai, Qing and Zhu, Jinpiao and Xiao, Nong}, title = {{Niacin promotes motor function recovery after spinal cord injury via Hcar2-dependent microglia immunometabolic regulation}}, journal = {Clinical and translational medicine}, year = {2026}, month = may, volume = {16}, number = {5}, pages = {e70683}, publisher = {Wiley}, issn = {2001-1326}, doi = {10.1002/ctm2.70683}, url = {https://doi.org/10.1002/ctm2.70683}, pmid = {42068080}, pmcid = {PMC13135113} }

RIS

TY - JOUR AU - Du, Hua AU - Zeng, Lingnian AU - Liu, Chan AU - Zhou, Huyao AU - Wang, Xia AU - Ai, Qing AU - Zhu, Jinpiao AU - Xiao, Nong TI - Niacin promotes motor function recovery after spinal cord injury via Hcar2-dependent microglia immunometabolic regulation T2 - Clinical and translational medicine J2 - Clin Transl Med PY - 2026 DA - 2026/05/01 VL - 16 IS - 5 SP - e70683 SN - 2001-1326 PB - Wiley DO - 10.1002/ctm2.70683 UR - https://doi.org/10.1002/ctm2.70683 LA - en ER -

CSL-JSON

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