RRC ID 79163
Author Wattrus SJ, Smith ML, Rodrigues CP, Hagedorn EJ, Kim JW, Budnik B, Zon LI.
Title Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality.
Journal Science
Abstract 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.
Volume 377(6613)
Pages 1413-1419
Published 2022-9-23
DOI 10.1126/science.abo4837
PMID 36137040
PMC PMC9524573
MeSH Animals Apoptosis* Calbindin 2 / genetics Calbindin 2 / physiology Calreticulin* / genetics Calreticulin* / metabolism Cell Communication* Clonal Hematopoiesis* / genetics Clonal Hematopoiesis* / physiology Embryo, Nonmammalian Hematopoietic Stem Cells* / physiology Macrophages* / physiology Zebrafish Zebrafish Proteins / genetics Zebrafish Proteins / physiology
IF 41.846
Zebrafish Tg(EF1α:mAG-zGem(1/100))rw0410h