Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality
Tissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform to initiate cancer. Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophag...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2022-09, Vol.377 (6613), p.1413-1419 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Wattrus, Samuel J Smith, Mackenzie L Rodrigues, Cecilia Pessoa Hagedorn, Elliott J Kim, Ji Wook Budnik, Bogdan Zon, Leonard I |
| description | Tissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform to initiate cancer. Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophages and nascent blood stem cells in zebrafish embryos. Macrophage interactions frequently led to either removal of cytoplasmic material and stem cell division or complete engulfment and stem cell death. Stressed stem cells were marked by surface Calreticulin, which stimulated macrophage interactions. Using cellular barcoding, we found that Calreticulin knock-down or embryonic macrophage depletion reduced the number of stem cell clones that established adult hematopoiesis. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality. |
| doi_str_mv | 10.1126/science.abo4837 |
| format | Article |
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Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophages and nascent blood stem cells in zebrafish embryos. Macrophage interactions frequently led to either removal of cytoplasmic material and stem cell division or complete engulfment and stem cell death. Stressed stem cells were marked by surface Calreticulin, which stimulated macrophage interactions. Using cellular barcoding, we found that Calreticulin knock-down or embryonic macrophage depletion reduced the number of stem cell clones that established adult hematopoiesis. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abo4837</identifier><identifier>PMID: 36137040</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Animals ; Apoptosis ; Blood cells ; Calbindin 2 - genetics ; Calbindin 2 - physiology ; Calreticulin - genetics ; Calreticulin - metabolism ; Cell Communication ; Cell surface ; Clonal Hematopoiesis - genetics ; Clonal Hematopoiesis - physiology ; Embryo cells ; Embryo, Nonmammalian ; Embryogenesis ; Embryonic growth stage ; Hematopoietic stem cells ; Hematopoietic Stem Cells - physiology ; Macrophages ; Macrophages - physiology ; Quality assurance ; Quality control ; Stem cells ; Zebrafish ; Zebrafish Proteins - genetics ; Zebrafish Proteins - physiology</subject><ispartof>Science (American Association for the Advancement of Science), 2022-09, Vol.377 (6613), p.1413-1419</ispartof><rights>Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. 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Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Blood cells</subject><subject>Calbindin 2 - genetics</subject><subject>Calbindin 2 - physiology</subject><subject>Calreticulin - genetics</subject><subject>Calreticulin - metabolism</subject><subject>Cell Communication</subject><subject>Cell surface</subject><subject>Clonal Hematopoiesis - genetics</subject><subject>Clonal Hematopoiesis - physiology</subject><subject>Embryo cells</subject><subject>Embryo, Nonmammalian</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - physiology</subject><subject>Macrophages</subject><subject>Macrophages - physiology</subject><subject>Quality assurance</subject><subject>Quality control</subject><subject>Stem cells</subject><subject>Zebrafish</subject><subject>Zebrafish Proteins - 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| subjects | Animals Apoptosis Blood cells Calbindin 2 - genetics Calbindin 2 - physiology Calreticulin - genetics Calreticulin - metabolism Cell Communication Cell surface Clonal Hematopoiesis - genetics Clonal Hematopoiesis - physiology Embryo cells Embryo, Nonmammalian Embryogenesis Embryonic growth stage Hematopoietic stem cells Hematopoietic Stem Cells - physiology Macrophages Macrophages - physiology Quality assurance Quality control Stem cells Zebrafish Zebrafish Proteins - genetics Zebrafish Proteins - physiology |
| title | Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality |
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