Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro
Summary: Myeloid cells, including brain-resident microglia and peripheral macrophages, play key roles in neurodegenerative diseases such as Alzheimer’s disease (AD). Studying their disease-associated states is limited by the lack of robust in vitro models. Here, we test whether a cytokine mix (inter...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725006801 |
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| author | Anna Podleśny-Drabiniok Carmen Romero-Molina Tulsi Patel Wen Yi See Yiyuan Liu Edoardo Marcora Alison M. Goate |
| author_facet | Anna Podleśny-Drabiniok Carmen Romero-Molina Tulsi Patel Wen Yi See Yiyuan Liu Edoardo Marcora Alison M. Goate |
| author_sort | Anna Podleśny-Drabiniok |
| collection | DOAJ |
| description | Summary: Myeloid cells, including brain-resident microglia and peripheral macrophages, play key roles in neurodegenerative diseases such as Alzheimer’s disease (AD). Studying their disease-associated states is limited by the lack of robust in vitro models. Here, we test whether a cytokine mix (interleukin [IL]-4, CSF1, IL-34, and transforming growth factor-β) reprograms human THP-1 macrophages toward AD-relevant phenotypes. This treatment induces significant transcriptomic changes, driving THP-1 macrophages toward a transcriptional state reminiscent of disease-associated microglia and lipid-associated macrophages (LAM), collectively referred to as DLAM. Transcriptome profiling reveals gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell RNA sequencing shows an increased proportion of DLAM clusters in cytokine mix-treated THP-1 macrophages. Functional assays demonstrate alterations in cell motility, phagocytosis, lysosomal activity, and metabolic profiles. These findings provide insights into cytokine-mediated reprogramming of macrophages toward disease-relevant states, highlighting their role in neurodegenerative diseases and potential for therapeutic development. |
| format | Article |
| id | doaj-art-e8f61c4aa13b4fa597d98d2eed86cb9f |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-e8f61c4aa13b4fa597d98d2eed86cb9f2025-08-20T02:35:36ZengElsevierCell Reports2211-12472025-07-0144711590910.1016/j.celrep.2025.115909Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitroAnna Podleśny-Drabiniok0Carmen Romero-Molina1Tulsi Patel2Wen Yi See3Yiyuan Liu4Edoardo Marcora5Alison M. Goate6Ronald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USARonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USARonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USARonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USARonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USARonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Sanford Grossman Interdisciplinary Program In Neural Circuitry and Immune Function, New York, NY 10029, USA; Corresponding authorRonald M. Loeb Center for Alzheimer’s Disease, Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Sanford Grossman Interdisciplinary Program In Neural Circuitry and Immune Function, New York, NY 10029, USA; Corresponding authorSummary: Myeloid cells, including brain-resident microglia and peripheral macrophages, play key roles in neurodegenerative diseases such as Alzheimer’s disease (AD). Studying their disease-associated states is limited by the lack of robust in vitro models. Here, we test whether a cytokine mix (interleukin [IL]-4, CSF1, IL-34, and transforming growth factor-β) reprograms human THP-1 macrophages toward AD-relevant phenotypes. This treatment induces significant transcriptomic changes, driving THP-1 macrophages toward a transcriptional state reminiscent of disease-associated microglia and lipid-associated macrophages (LAM), collectively referred to as DLAM. Transcriptome profiling reveals gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell RNA sequencing shows an increased proportion of DLAM clusters in cytokine mix-treated THP-1 macrophages. Functional assays demonstrate alterations in cell motility, phagocytosis, lysosomal activity, and metabolic profiles. These findings provide insights into cytokine-mediated reprogramming of macrophages toward disease-relevant states, highlighting their role in neurodegenerative diseases and potential for therapeutic development.http://www.sciencedirect.com/science/article/pii/S2211124725006801CP: NeuroscienceCP: Immunology |
| spellingShingle | Anna Podleśny-Drabiniok Carmen Romero-Molina Tulsi Patel Wen Yi See Yiyuan Liu Edoardo Marcora Alison M. Goate Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro Cell Reports CP: Neuroscience CP: Immunology |
| title | Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro |
| title_full | Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro |
| title_fullStr | Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro |
| title_full_unstemmed | Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro |
| title_short | Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypes in vitro |
| title_sort | cytokine induced reprogramming of human macrophages toward alzheimer s disease relevant molecular and cellular phenotypes in vitro |
| topic | CP: Neuroscience CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725006801 |
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