Derivation of extra-embryonic and intra-embryonic macrophage lineages from human pluripotent stem cells.
Autor: | Bredemeyer AL; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Amrute JM; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Koenig AL; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Idol RA; Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA., He L; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Luff SA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY 10029, USA., Dege C; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO 63110, USA., Leid JM; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Schilling JD; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA., Hinson JT; Departments of Cardiology, Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA.; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA., Dinauer MC; Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA., Sturgeon CM; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY 10029, USA.; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO 63110, USA., Lavine KJ; Center for Cardiovascular Research, Departmental of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.; Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA. |
---|---|
Jazyk: | angličtina |
Zdroj: | Development (Cambridge, England) [Development] 2022 Apr 15; Vol. 149 (8). Date of Electronic Publication: 2022 May 03. |
DOI: | 10.1242/dev.200016 |
Abstrakt: | Tissue-resident macrophages are increasingly recognized as important determinants of organ homeostasis, tissue repair, remodeling and regeneration. Although the ontogeny and function of tissue-resident macrophages has been identified as distinct from postnatal hematopoiesis, the inability to specify, in vitro, similar populations that recapitulate these developmental waves has limited our ability to study their function and potential for regenerative applications. We took advantage of the concept that tissue-resident macrophages and monocyte-derived macrophages originate from distinct extra-embryonic and definitive hematopoietic lineages to devise a system to generate pure cultures of macrophages that resemble tissue-resident or monocyte-derived subsets. We demonstrate that human pluripotent stem cell-derived extra-embryonic-like and intra-embryonic-like hematopoietic progenitors differentiate into morphologically, transcriptionally and functionally distinct macrophage populations. Single-cell RNA sequencing of developing and mature cultures uncovered distinct developmental trajectories and gene expression programs of macrophages derived from extra-embryonic-like and intra-embryonic-like hematopoietic progenitors. These findings establish a resource for the generation of human tissue resident-like macrophages to study their specification and function under defined conditions and to explore their potential use in tissue engineering and regenerative medicine applications. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.) |
Databáze: | MEDLINE |
Externí odkaz: |