{"title":"Single transcription factor efficiently leads human induced pluripotent stem cells to functional microglia.","authors":"Iki Sonn, Fumiko Honda-Ozaki, Sho Yoshimatsu, Satoru Morimoto, Hirotaka Watanabe, Hideyuki Okano","doi":"10.1186/s41232-022-00201-1","DOIUrl":"https://doi.org/10.1186/s41232-022-00201-1","url":null,"abstract":"<p><strong>Background: </strong>Microglia are innate immune cells that are the only residential macrophages in the central nervous system. They play vital physiological roles in the adult brain and during development. Microglia are particularly in the spotlight because many genetic risk factors recently identified for neurodegenerative diseases are largely expressed in microglia. Rare polymorphisms in these risk alleles lead to abnormal activity of microglia under traumatic or disease conditions.</p><p><strong>Methods: </strong>In the present study, to investigate the multifaceted functions of human microglia, we established a novel robust protocol to generate microglia from human induced pluripotent stem cells (hiPSCs) using a combination of cytokines and small chemicals essential for microglia ontogeny. Moreover, we highly enhanced the microglial differentiation efficiency by forcing the expression of PU.1, a crucial transcription factor for microglial development, during posterior mesoderm differentiation.</p><p><strong>Results: </strong>By our novel method, we demonstrated the generation of a greater number of hiPSC-derived microglia (hiMGLs, approximately 120-folds) than the prior methods (at most 40-folds). Over 90% of the hiMGLs expressed microglia-specific markers, such as CX3CR1 and IBA-1. Whole-transcriptome analysis revealed that these hiMGLs are similar to human primary microglia but differ from monocytes/macrophages. Furthermore, the specific physiological functions of microglia were confirmed through indices of lipopolysaccharide responsiveness, phagocytotic ability, and inflammasome formation. By co-culturing these hiMGLs with mouse primary neurons, we demonstrated that hiMGLs can regulate the activity and maturation of neurons.</p><p><strong>Conclusions: </strong>In this study, our new simple, rapid, and highly efficient method for generating microglia from hiPSCs will prove useful for future investigations on microglia in both physiological and disease conditions, as well as for drug discovery.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":"20"},"PeriodicalIF":8.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40561631","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}
{"title":"A case of refractory systemic lupus erythematosus with monocytosis exhibiting somatic KRAS mutation","authors":"S. Law, S. Akizuki, A. Morinobu, K. Ohmura","doi":"10.1186/s41232-022-00195-w","DOIUrl":"https://doi.org/10.1186/s41232-022-00195-w","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65781005","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":"Editorial: Towards a better understanding of the physiology of the lymphatics","authors":"Masayuki Miyasaka","doi":"10.1186/s41232-022-00200-2","DOIUrl":"https://doi.org/10.1186/s41232-022-00200-2","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65781267","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}
S. Miyagi, Y. Kato, Ayako Watanabe, K. Miyamoto, Rintaro Yoshikawa, K. Hagiya, D. Hirano, Y. Matsuzaki
{"title":"Generation of a BAC transgenic mouse strain that expresses CreERT and a fluorescent protein under the transcriptional control of the Fzd5 locus","authors":"S. Miyagi, Y. Kato, Ayako Watanabe, K. Miyamoto, Rintaro Yoshikawa, K. Hagiya, D. Hirano, Y. Matsuzaki","doi":"10.1186/s41232-022-00194-x","DOIUrl":"https://doi.org/10.1186/s41232-022-00194-x","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48265623","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}