{"title":"Cancer ego-system in glioma: an iron-replenishing niche network systemically self-organized by cancer stem cells.","authors":"Kouichi Tabu, Tetsuya Taga","doi":"10.1186/s41232-022-00240-8","DOIUrl":"https://doi.org/10.1186/s41232-022-00240-8","url":null,"abstract":"<p><p>For all living organisms, the adaptation to outside environments is an essential determinant to survive natural and artificial selections and to sustain the whole ecosystem intact with functional biodiversity. Likewise, cancer cells have similar characteristics that evade not only stresses from the host-internal innate and adaptive immune systems but also those from host-externally administered therapeutic interventions. Such selfish characteristics of cancer cells lead to the formation of cancerous ecosystem with a wide variety of phenotypic heterogeneity, which should be called cancer \"egosystem\" from the host point of view. Recently increasing evidence demonstrates that cancer stem cells (CSCs) are responsible for this cancer egosystem by effectively exploiting host inflammatory and hematopoietic cells and thereby reconstructing their own advantageous niches, which may well be a driving force in cancer recurrence. CSCs are further likely to render multiple niches mutually interconnected and cooperating as a network to support back CSCs themselves. Here, we summarize a recently identified iron-replenishing niche network self-organized by glioma CSCs (GSCs) through remote regulation of host myeloid and erythroid lineage cells. GSCs recruit bone marrow (BM)-derived inflammatory monocytes into tumor parenchyma, facilitate their differentiation into macrophages (Mφs) and skew their polarization into pro-tumoral phenotype, i.e., tumor-associated Mφs (TAMs). Meanwhile, GSCs distantly enhance erythropoiesis in host hematopoietic organs like BM and spleen potentially by secreting some soluble mediators that maintain continuous supply of erythrocytes within tumors. In addition, as normal red pulp Mφs (RPMs) under steady state conditions in spleen recycle iron by phagocytosing the aged or damaged erythrocytes (a/dECs) and release it in time of need, TAMs at least in gliomas phagocytose the hemorrhaged erythrocytes within tumors and potentially serve as a source of iron, an important nutrient indispensable to GSC survival and glioma progression. Taken together, these studies provide the substantial evidence that CSCs have a unique strategy to orchestrate multiple niches as an ecosystem that threatens the host living, which in this sense must be an egosystem. Targeting such an adaptive subpopulation of CSCs could achieve drastic disturbance of the CSC niches and subsequent extinction of malignant neoplasms.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":"54"},"PeriodicalIF":8.1,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19.","authors":"Takahiro Kawasaki, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Mari Nogami-Itoh, Takanori Matsuki, Hiroshi Kida, Takatoshi Enomoto, Reina Hara, Yoshimi Noda, Yuichi Adachi, Takayuki Niitsu, Saori Amiya, Yuta Yamaguchi, Teruaki Murakami, Yasuhiro Kato, Takayoshi Morita, Hanako Yoshimura, Makoto Yamamoto, Daisuke Nakatsubo, Kotaro Miyake, Takayuki Shiroyama, Haruhiko Hirata, Jun Adachi, Yukinori Okada, Atsushi Kumanogoh","doi":"10.1186/s41232-022-00243-5","DOIUrl":"https://doi.org/10.1186/s41232-022-00243-5","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease 2019 (COVID-19) pandemic is widespread; however, accurate predictors of refractory cases have not yet been established. Circulating extracellular vesicles, involved in many pathological processes, are ideal resources for biomarker exploration.</p><p><strong>Methods: </strong>To identify potential serum biomarkers and examine the proteins associated with the pathogenesis of refractory COVID-19, we conducted high-coverage proteomics on serum extracellular vesicles collected from 12 patients with COVID-19 at different disease severity levels and 4 healthy controls. Furthermore, single-cell RNA sequencing of peripheral blood mononuclear cells collected from 10 patients with COVID-19 and 5 healthy controls was performed.</p><p><strong>Results: </strong>Among the 3046 extracellular vesicle proteins that were identified, expression of MACROH2A1 was significantly elevated in refractory cases compared to non-refractory cases; moreover, its expression was increased according to disease severity. In single-cell RNA sequencing of peripheral blood mononuclear cells, the expression of MACROH2A1 was localized to monocytes and elevated in critical cases. Consistently, single-nucleus RNA sequencing of lung tissues revealed that MACROH2A1 was highly expressed in monocytes and macrophages and was significantly elevated in fatal COVID-19. Moreover, molecular network analysis showed that pathways such as \"estrogen signaling pathway,\" \"p160 steroid receptor coactivator (SRC) signaling pathway,\" and \"transcriptional regulation by STAT\" were enriched in the transcriptome of monocytes in the peripheral blood mononuclear cells and lungs, and they were also commonly enriched in extracellular vesicle proteomics.</p><p><strong>Conclusions: </strong>Our findings highlight that MACROH2A1 in extracellular vesicles is a potential biomarker of refractory COVID-19 and may reflect the pathogenesis of COVID-19 in monocytes.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":"53"},"PeriodicalIF":8.1,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current understanding of T cell immunity against SARS-CoV-2.","authors":"Xiuyuan Lu, Sho Yamasaki","doi":"10.1186/s41232-022-00242-6","DOIUrl":"https://doi.org/10.1186/s41232-022-00242-6","url":null,"abstract":"<p><p>As an important part of adaptive immunity, T cells are indispensable in the defense against pathogens including viruses. SARS-CoV-2 is a new human coronavirus that occurred at the end of 2019 and has caused the COVID-19 pandemic. Nevertheless, most of the infected patients recovered without any antiviral therapies, suggesting an effective immunity developed in the bodies. T cell immunity responds upon SARS-CoV-2 infection or vaccination and plays crucial roles in eliminating the viruses and generating T cell memory. Specifically, a subpopulation of CD4<sup>+</sup> T cells could support the production of anti-SARS-CoV-2 antibodies, and cytotoxic CD8<sup>+</sup> T cells are also protective against the infection. SARS-CoV-2-recognizing T cells could be detected in SARS-CoV-2-unexposed donors, but the role of these cross-reactive T cells is still in debate. T cell responses could be diverse across individuals, mainly due to the polymorphism of HLAs. Thus, compared to antibodies, T cell responses are generally less affected by the mutations of SARS-CoV-2 variants. Up to now, a huge number of studies on SARS-CoV-2-responsive T cells have been published. In this review, we introduced some major findings addressing the questions in the main aspects about T cell responses elicited by SARS-CoV-2, to summarize the current understanding of COVID-19.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":"51"},"PeriodicalIF":8.1,"publicationDate":"2022-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10694571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation.","authors":"Sakurako Kobayashi, Nobuhiko Ogasawara, Satoshi Watanabe, Yosuke Yoneyama, Sakura Kirino, Yui Hiraguri, Masami Inoue, Sayaka Nagata, Yoshimi Okamoto-Uchida, Satoshi Kofuji, Hiromichi Shimizu, Go Ito, Tomohiro Mizutani, Shinichi Yamauchi, Yusuke Kinugasa, Yoshihito Kano, Yasuhiro Nemoto, Mamoru Watanabe, Kiichiro Tsuchiya, Hiroshi Nishina, Ryuichi Okamoto, Shiro Yui","doi":"10.1186/s41232-022-00237-3","DOIUrl":"https://doi.org/10.1186/s41232-022-00237-3","url":null,"abstract":"<p><strong>Background: </strong>The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms of intestinal epithelium during inflammation. We previously revealed that the remodeling of mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion of intestinal/colonic epithelial cells covering the wound bed towards fetal-like progenitors. To fully elucidate the mechanisms underlying the link between extracellular matrix (ECM) remodeling of mesenchyme and fetal-like reprogramming of epithelial cells, it is critical to understand how collagen type I influence the phenotype of epithelial cells. In this study, we utilize collagen sphere, which is the epithelial organoids cultured in purified collagen type I, to understand the mechanisms of the inflammatory associated reprogramming. Resolving the entire landscape of regulatory networks of the collagen sphere is useful to dissect the reprogrammed signature of the intestinal epithelium.</p><p><strong>Methods: </strong>We performed microarray, RNA-seq, and ATAC-seq analyses of the murine collagen sphere in comparison with Matrigel organoid and fetal enterosphere (FEnS). We subsequently cultured human colon epithelium in collagen type I and performed RNA-seq analysis. The enriched genes were validated by gene expression comparison between published gene sets and immunofluorescence in pathological specimens of ulcerative colitis (UC).</p><p><strong>Results: </strong>The murine collagen sphere was confirmed to have inflammatory and regenerative signatures from RNA-seq analysis. ATAC-seq analysis confirmed that the YAP/TAZ-TEAD axis plays a central role in the induction of the distinctive signature. Among them, TAZ has implied its relevant role in the process of reprogramming and the ATAC-based motif analysis demonstrated not only Tead proteins, but also Fra1 and Runx2, which are highly enriched in the collagen sphere. Additionally, the human collagen sphere also showed a highly significant enrichment of both inflammatory and fetal-like signatures. Immunofluorescence staining confirmed that the representative genes in the human collagen sphere were highly expressed in the inflammatory region of ulcerative colitis.</p><p><strong>Conclusions: </strong>Collagen type I showed a significant influence in the acquisition of the reprogrammed inflammatory signature in both mice and humans. Dissection of the cell fate conversion and its mechanisms shown in this study can enhance our understanding of how the epithelial signature of inflammation is influenced by the ECM niche.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":"49"},"PeriodicalIF":8.1,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoshimasa Tanaka, M. Nishikawa, Kaho Kamisaki, Saki Hachiya, Moeka Nakamura, Takahiro Kuwazuru, S. Tanimura, K. Soyano, K. Takeda
{"title":"Marine-derived microbes and molecules for drug discovery","authors":"Yoshimasa Tanaka, M. Nishikawa, Kaho Kamisaki, Saki Hachiya, Moeka Nakamura, Takahiro Kuwazuru, S. Tanimura, K. Soyano, K. Takeda","doi":"10.1186/s41232-022-00207-9","DOIUrl":"https://doi.org/10.1186/s41232-022-00207-9","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65781297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shin-ichiro Hiraga, T. Itokazu, Mariko Nishibe, T. Yamashita
{"title":"Neuroplasticity related to chronic pain and its modulation by microglia","authors":"Shin-ichiro Hiraga, T. Itokazu, Mariko Nishibe, T. Yamashita","doi":"10.1186/s41232-022-00199-6","DOIUrl":"https://doi.org/10.1186/s41232-022-00199-6","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41555824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The superficial zone of articular cartilage","authors":"Taku Saito","doi":"10.1186/s41232-022-00202-0","DOIUrl":"https://doi.org/10.1186/s41232-022-00202-0","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42522311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Hachiya, Miyako Tanaka, Michiko Itoh, T. Suganami
{"title":"Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome","authors":"R. Hachiya, Miyako Tanaka, Michiko Itoh, T. Suganami","doi":"10.1186/s41232-022-00198-7","DOIUrl":"https://doi.org/10.1186/s41232-022-00198-7","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46265661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salwa Suliman, A. Mieszkowska, J. Folkert, Neha Rana, Samih Mohamed-Ahmed, Tiziana Fuoco, A. Finne‐Wistrand, K. Dirscherl, Bodil Jørgensen, K. Mustafa, Katarzyna Gurzawska-Comis
{"title":"Immune-instructive copolymer scaffolds using plant-derived nanoparticles to promote bone regeneration","authors":"Salwa Suliman, A. Mieszkowska, J. Folkert, Neha Rana, Samih Mohamed-Ahmed, Tiziana Fuoco, A. Finne‐Wistrand, K. Dirscherl, Bodil Jørgensen, K. Mustafa, Katarzyna Gurzawska-Comis","doi":"10.1186/s41232-022-00196-9","DOIUrl":"https://doi.org/10.1186/s41232-022-00196-9","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47819573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?","authors":"Naoko Ohtani","doi":"10.1186/s41232-022-00197-8","DOIUrl":"https://doi.org/10.1186/s41232-022-00197-8","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43183417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}