Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality.

Autor: Wattrus SJ; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA., Smith ML; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA., Rodrigues CP; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA., Hagedorn EJ; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA., Kim JW; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA., Budnik B; Mass Spectrometry and Proteomics Resource Laboratory, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, MA, USA., Zon LI; Howard Hughes Medical Institute, Boston Children's Hospital Boston, MA, USA.; Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Sep 23; Vol. 377 (6613), pp. 1413-1419. Date of Electronic Publication: 2022 Sep 22.
DOI: 10.1126/science.abo4837
Abstrakt: 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.
Databáze: MEDLINE
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