학술논문
Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon.
Document Type
Academic Journal
Author
Múnera JO; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: munera@musc.edu.; Kechele DO; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Bouffi C; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Qu N; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.; Jing R; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.; Maity P; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.; Enriquez JR; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Han L; Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.; Campbell I; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Mahe MM; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; McCauley HA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Zhang X; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Sundaram N; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Hudson JR; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Zarsozo-Lacoste A; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Pradhan S; Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA.; Tominaga K; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Sanchez JG; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Weiss AA; Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA.; Chatuvedi P; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.; Spence JR; Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.; Hachimi M; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.; North T; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.; Daley GQ; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.; Mayhew CN; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Pluripotent Stem Cell Facility, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Hu YC; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Pluripotent Stem Cell Facility, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Takebe T; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Helmrath MA; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Wells JM; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: james.wells@cchmc.org.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101311472 Publication Model: Print Cited Medium: Internet ISSN: 1875-9777 (Electronic) Linking ISSN: 18759777 NLM ISO Abbreviation: Cell Stem Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages. HCO macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals and were able to phagocytose and mount a robust response to pathogenic bacteria. When transplanted into mice, HCO macrophages were maintained within the colonic organoid tissue, established a close association with the colonic epithelium, and were not displaced by the host bone-marrow-derived macrophages. These studies suggest that HE in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 Elsevier Inc. All rights reserved.)