Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 43 min ago
Peer-reviewedCC BYFrontiers in Cell and Developmental Biology

Clinical, single-cell, and spatial transcriptomic integration identifies an RCD-high inflammatory myeloid program for early neurological deterioration and outcome stratification after acute ischemic stroke

  • Nan Jia1
  • Jianqi Li2
  • He Yang3
  • Hongfan Huo1
  • Xinxin Li4
  • Yaping Yan5
  • Biao Hua1
  • Liang Qin6
  • Li Ling1
6 affiliations
  1. 1Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei, China
  2. 2Department of Emergency Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, China
  3. 3Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China
  4. 4Department of Neurology, Baoding No. 1 Central Hospital, Baoding, Hebei, China
  5. 5Department of Rheumatology and Immunology, Baoding No. 1 Central Hospital, Baoding, Hebei, China
  6. 6Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, China
Read full textDOICite

Abstract

BackgroundNeuroinflammation and regulated cell death (RCD) are important components of secondary injury after acute ischemic stroke (AIS). However, the myeloid cell states involved in these processes and their spatial organization within ischemic brain tissue remain incompletely understood. This study aimed to characterize RCD-associated inflammatory myeloid remodeling by integrating clinical observations with single-cell and spatial transcriptomic analyses.MethodsWe retrospectively analyzed 367 patients with anterior-circulation AIS, comprising earlier (n = 216) and later (n = 151) admission cohorts. Clinical characteristics, inflammatory markers, early neurological deterioration (END), and 90-day functional outcomes were evaluated. Public mouse single-cell, single-nucleus, bulk, and spatial transcriptomic datasets (GSE174574 and GSE233815) were integrated to investigate RCD-associated cellular heterogeneity, myeloid-state transitions, transcriptional regulation, metabolic programs, intercellular communication, and spatial distributions.ResultsEND occurred in 51 patients (13.9%), and 127 (34.6%) experienced unfavorable 90-day functional outcomes. Unfavorable outcomes were associated with greater neurological severity and higher admission neutrophil-to-lymphocyte ratios and C-reactive protein levels. Transcriptomic analyses identified a distinct RCD-high inflammatory macrophage state characterized by coordinated expression of inflammasome/pyroptosis-associated genes (Nlrp3, Pycard, Casp1, Gsdmd, and Il1b) and phagocytic markers (Cd68, Mertk, and Ctsb). This state was concentrated at later inferred myeloid pseudotime and exhibited NF-κB/STAT-associated regulatory programs, metabolic remodeling, and extensive predicted interactions with glial and vascular cells. Spatial transcriptomic mapping revealed localized RCD-high macrophage-associated signals in post-ischemic brain tissue, with partially overlapping distributions across related myeloid states.ConclusionThis study identifies an RCD-high inflammatory macrophage state characterized by the convergence of cell-death-associated, phagocytic, and metabolic stress-response programs following cerebral ischemia. Its transcriptional characteristics, predicted intercellular interactions, and heterogeneous spatial distribution provide new insights into post-ischemic myeloid remodeling and the cellular organization of neuroinflammation.

Related

  1. Integrative Transcriptomic and Network Analyses Reveal Common Molecular Signatures and Turmeric‐Derived Common Therapeutic Candidates for Neurological Diseases
    Sumi Rani Bayragi, Riday Hossain, Md. Zohurul Islam +2
    BioMed Research InternationalPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMC
  2. Integration of Transcriptomic and Metabolomic Profiling as a Source of Insight into Key Candidate Genes and Metabolic Pathways Associated with Maize Resistance to Fusarium spp.
    Maciej Lenort, Agnieszka Tomkowiak, Jan Bocianowski +7
    International Journal of Molecular SciencesPeer-reviewedCC BY 4.0General biochemistryCrossref
  3. Integrated transcriptomic analysis identifies an AKT1-associated metabolic-inflammatory signature in osteoporosis.
    Chenglong Bao, Ronggui Hu
    Clinical and experimental medicinePeer-reviewedCC BY-NC-NDFull textMolecular biology & gene regulationEurope PMC
  4. Interferon-Associated Inflammatory Remodeling and Oxidative Metabolic Repression Define the Skeletal Muscle Transcriptomic Landscape of δ-Sarcoglycan Deficiency
    Amairani Cancino-Bello, Mauricio Hernández-Somilleda, Erick Bahena-Culhuac +4
    BiomoleculesPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCrossrefEurope PMCDOAJ
  5. Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration
    Bjoern Schroeder, George M.H. Birchenough, Marcus Ståhlman +4
    Cell Host & MicrobePeer-reviewedLicence not statedFull text713 citedMolecular biology & gene regulationHAL

Cite

BibTeXRIS
BibTeX
@article{jia2026clinical,
  title = {{Clinical, single-cell, and spatial transcriptomic integration identifies an RCD-high inflammatory myeloid program for early neurological deterioration and outcome stratification after acute ischemic stroke}},
  author = {Nan Jia and Jianqi Li and He Yang and Hongfan Huo and Xinxin Li and Yaping Yan and Biao Hua and Liang Qin and Li Ling},
  journal = {Frontiers in Cell and Developmental Biology},
  year = {2026},
  month = nov,
  doi = {10.3389/fcell.2026.1981135},
  url = {https://doi.org/10.3389/fcell.2026.1981135},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Clinical, single-cell, and spatial transcriptomic integration identifies an RCD-high inflammatory myeloid program for early neurological deterioration and outcome stratification after acute ischemic stroke
AU  - Nan Jia
AU  - Jianqi Li
AU  - He Yang
AU  - Hongfan Huo
AU  - Xinxin Li
AU  - Yaping Yan
AU  - Biao Hua
AU  - Liang Qin
AU  - Li Ling
PY  - 2026
DA  - 2026/11/05
JO  - Frontiers in Cell and Developmental Biology
DO  - 10.3389/fcell.2026.1981135
UR  - https://doi.org/10.3389/fcell.2026.1981135
AB  - BackgroundNeuroinflammation and regulated cell death (RCD) are important components of secondary injury after acute ischemic stroke (AIS). However, the myeloid cell states involved in these processes and their spatial organization within ischemic brain tissue remain incompletely understood. This study aimed to characterize RCD-associated inflammatory myeloid remodeling by integrating clinical observations with single-cell and spatial transcriptomic analyses.MethodsWe retrospectively analyzed 367 patients with anterior-circulation AIS, comprising earlier (n = 216) and later (n = 151) admission cohorts. Clinical characteristics, inflammatory markers, early neurological deterioration (END), and 90-day functional outcomes were evaluated. Public mouse single-cell, single-nucleus, bulk, and spatial transcriptomic datasets (GSE174574 and GSE233815) were integrated to investigate RCD-associated cellular heterogeneity, myeloid-state transitions, transcriptional regulation, metabolic programs, intercellular communication, and spatial distributions.ResultsEND occurred in 51 patients (13.9%), and 127 (34.6%) experienced unfavorable 90-day functional outcomes. Unfavorable outcomes were associated with greater neurological severity and higher admission neutrophil-to-lymphocyte ratios and C-reactive protein levels. Transcriptomic analyses identified a distinct RCD-high inflammatory macrophage state characterized by coordinated expression of inflammasome/pyroptosis-associated genes (Nlrp3, Pycard, Casp1, Gsdmd, and Il1b) and phagocytic markers (Cd68, Mertk, and Ctsb). This state was concentrated at later inferred myeloid pseudotime and exhibited NF-κB/STAT-associated regulatory programs, metabolic remodeling, and extensive predicted interactions with glial and vascular cells. Spatial transcriptomic mapping revealed localized RCD-high macrophage-associated signals in post-ischemic brain tissue, with partially overlapping distributions across related myeloid states.ConclusionThis study identifies an RCD-high inflammatory macrophage state characterized by the convergence of cell-death-associated, phagocytic, and metabolic stress-response programs following cerebral ischemia. Its transcriptional characteristics, predicted intercellular interactions, and heterogeneous spatial distribution provide new insights into post-ischemic myeloid remodeling and the cellular organization of neuroinflammation.
SN  - 2296-634X
ER  -