{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:59:20Z","timestamp":1768215560193,"version":"3.49.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The Axolotl (\n                      <jats:italic>Ambystoma mexicanum<\/jats:italic>\n                      ) offers a deep insight into brain regeneration by fully reconstructing its telencephalon post-injury, a capability that most vertebrates do not have. This study aimed to identify hub genes (highest-weighted genes) underlying this process and to map their cell location by analyzing spatiotemporal transcriptomic data using high-dimensional weighted gene co-expression network analysis, integrating protein-protein interaction networks, and cross-validating findings through literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 180 hub genes across the regeneration timeline, including several with conserved orthologs previously reported in vertebrate regeneration models. Among these candidates, TRH (Thyrotropin-Releasing Hormone) displayed the most consistent spatiotemporal pattern, appearing repeatedly as a hub gene and localizing to MSN enriched regions at multiple stages. TRH is broadly characterized in vertebrates as a neuroendocrine peptide with roles in hormonal signaling, and MSNs are known to respond to a variety of hormonal and neuropeptidergic cues. In our dataset, this background provides additional perspective on the transcriptional configurations in which TRH appears. Other hub genes showed stage\/cell specific patterns, together outlining a heterogeneous and dynamic landscape of transcriptional states detected during telencephalon regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a descriptive map of gene co-expression dynamics during axolotl telencephalon regeneration. By integrating hdWGCNA, spatial transcriptomics, and network-based context, we identify hub genes and transcriptional states associated with injury response, including a persistent TRH linked MSN state. These findings offer a foundation for future experimental studies aimed at elucidating the molecular basis of axolotl brain repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2025.1697212","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:51:38Z","timestamp":1768204298000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High-dimensional co-expression network analysis reveals persistent TRH gene expression throughout axolotl telencephalon regeneration"],"prefix":"10.3389","volume":"5","author":[{"given":"Iveth","family":"G\u00f3mez-Morales","sequence":"first","affiliation":[]},{"given":"Adriana P.","family":"Mendizabal-Ruiz","sequence":"additional","affiliation":[]},{"given":"J. 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