Journal article
Derivation of extra-embryonic and intra-embryonic macrophage lineages from human pluripotent stem cells
Development (Cambridge), Vol.149(8), dev200016
04/15/2022
DOI: 10.1242/dev.200016
PMID: 35178561
Abstract
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.
Details
- Title: Subtitle
- Derivation of extra-embryonic and intra-embryonic macrophage lineages from human pluripotent stem cells
- Creators
- Andrea L Bredemeyer - Washington University in St. LouisJunedh M Amrute - Washington University in St. LouisAndrew L Koenig - Washington University in St. LouisRachel A Idol - Washington University in St. LouisLi He - Washington University in St. LouisStephanie A Luff - Icahn School of Medicine at Mount SinaiCarissa Dege - Washington University in St. LouisJamison M Leid - Washington University in St. LouisJoel D Schilling - Washington University in St. LouisJ Travis Hinson - Jackson LaboratoryMary C Dinauer - Washington University in St. LouisChristopher M Sturgeon - Washington University in St. LouisKory J Lavine - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.149(8), dev200016
- DOI
- 10.1242/dev.200016
- PMID
- 35178561
- ISSN
- 0950-1991
- eISSN
- 1477-9129
- Grant note
- R21 AI148877 / NIAID NIH HHS R01 HL139714 / NHLBI NIH HHS U01 HL156349 / NHLBI NIH HHS R35 HL161185 / NHLBI NIH HHS U01 EB028898 / NIBIB NIH HHS R01 HL138466 / NHLBI NIH HHS R01 HL151777 / NHLBI NIH HHS R01 HL145290 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/15/2022
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161355402771
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