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This study endeavors to shed light on the complex cellular and molecular alterations that occur in the brains of a mouse model with SAE, ultimately unraveling the underlying mechanisms of this condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We established a murine model using intraperitoneal injection of lipopolysaccharide (LPS) in wild type and\n                      <jats:italic>Anxa1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice and collected brain tissues for analysis at 0-hour, 12-hour, 24-hour, and 72-hour post-injection. Utilizing advanced techniques such as single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq, we conducted a comprehensive characterization of the cellular responses and molecular patterns within the brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study uncovered notable temporal differences in the response to LPS challenge between Anxa1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (annexin A1 knockout) and wild type mice, specifically at the 12-hour and 24-hour time points following injection. We observed a significant increase in the proportion of Astro-2 and Micro-2 cells in these mice. These cells exhibited a colocalization pattern with the vascular subtype Vas-1, forming a distinct region known as V1A2M2, where Astro-2 and Micro-2 cells surrounded Vas-1. Moreover, through further analysis, we discovered significant upregulation of ligands and receptors such as\n                      <jats:italic>Timp1-Cd63<\/jats:italic>\n                      ,\n                      <jats:italic>Timp1-Itgb1<\/jats:italic>\n                      ,\n                      <jats:italic>Timp1-Lrp1<\/jats:italic>\n                      , as well as\n                      <jats:italic>Ccl2-Ackr1<\/jats:italic>\n                      and\n                      <jats:italic>Cxcl2-Ackr1<\/jats:italic>\n                      within this region. In addition, we observed a notable increase in the expression of\n                      <jats:italic>Cd14-Itgb1<\/jats:italic>\n                      ,\n                      <jats:italic>Cd14-Tlr2<\/jats:italic>\n                      , and\n                      <jats:italic>Cd14-C3ar1<\/jats:italic>\n                      in regions enriched with Micro-2 cells. Additionally,\n                      <jats:italic>Cxcl10-Sdc4<\/jats:italic>\n                      showed broad upregulation in brain regions containing both Micro-2 and Astro-2 cells. Notably, upon LPS challenge, there was an observed increase in\n                      <jats:italic>Anxa1<\/jats:italic>\n                      expression in the mouse brain. Furthermore, our study revealed a noteworthy increase in mortality rates following\n                      <jats:italic>Anxa1<\/jats:italic>\n                      knockdown. However, we did not observe substantial differences in the types, numbers, or distribution of other brain cells between Anxa1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and wildtype mice over time. Nevertheless, when comparing the 24-hour post LPS injection time point, we observed a significant decrease in the proportion and distribution of Micro-2 and Astro-2 cells in the vicinity of blood vessels in Anxa1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Additionally, we noted reduced expression levels of several ligand-receptor pairs including\n                      <jats:italic>Cd14-Tlr2<\/jats:italic>\n                      ,\n                      <jats:italic>Cd14-C3ar1<\/jats:italic>\n                      ,\n                      <jats:italic>Cd14-Itgb1<\/jats:italic>\n                      ,\n                      <jats:italic>Cxcl10-Sdc4<\/jats:italic>\n                      ,\n                      <jats:italic>Ccl2-Ackr1<\/jats:italic>\n                      , and\n                      <jats:italic>Cxcl2-Ackr1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      By combining snRNA-seq and Stereo-seq techniques, our study successfully identified a distinctive cellular colocalization, referred to as a special pathological niche, comprising Astro-2, Micro-2, and Vas-1 cells. Furthermore, we observed an upregulation of ligand-receptor pairs within this niche. These findings suggest a potential association between this cellular arrangement and the underlying mechanisms contributing to SAE or the increased mortality observed in\n                      <jats:italic>Anxa1<\/jats:italic>\n                      knockdown mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-024-03161-0","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T13:02:00Z","timestamp":1720011720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy"],"prefix":"10.1186","volume":"21","author":[{"given":"Yanyan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjun","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingsen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"issue":"1","key":"3161_CR1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s13054-018-2157-z","volume":"22","author":"KE Rudd","year":"2018","unstructured":"Rudd KE, et al. 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