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

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.

SUBMITTER: Wattrus SJ

PROVIDER: S-EPMC9524573 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Wattrus Samuel J SJ Smith Mackenzie L ML Rodrigues Cecilia Pessoa CP Hagedorn Elliott J EJ Kim Ji Wook JW Budnik Bogdan B Zon Leonard I LI

Science (New York, N.Y.) 20220922 6613

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 ...[more]

PMID: 36137040

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

Project description:There are no described quality assurance mechanisms for newly formed stem cells. We observed intimate interactions between macrophages and blood stem cells in zebrafish embryos. Stressed stem cells were marked by surface Calreticulin, which stimulates macrophage interaction as an eat me signal. Macrophage-stem cell interactions either lead to removal of cytoplasmic material and stem cell proliferation or resulted in complete stem cell engulfment. Calreticulin knock down or embryonic macrophage depletion reduced the number of stem cell clones into adulthood. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.

2022-02-04 | MSV000088780 | MassIVE

Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [macrophages]

Project 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 blood stem cells in zebrafish embryos. Stressed stem cells were marked by surface Calreticulin, which stimulates macrophage interaction as an “eat me” signal. Macrophage-stem cell interactions either lead to removal of cytoplasmic material and stem cell proliferation or resulted in complete stem cell engulfment. Using cellular barcoding, we found that calreticulin knock-down or embryonic macrophage depletion substantially reduced the number of stem cell clones into adulthood. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.

2022-10-19 | GSE196551 | GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-19 | GSE196553 | GEO

Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [HSCP]

2022-10-19 | GSE196552 | GEO

Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [macrophages]

Project description:Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [macrophages]

| PRJNA805357 | ENA

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

Project description:Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality

| PRJNA805354 | ENA

Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [HSCP]

Project description:Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality [HSCP]

| PRJNA805356 | ENA

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state.

Project description:ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.

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Embryonic stem cell-derived hematopoietic stem cells.

Project description:Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4, we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites confirms a common stem cell origin of lymphoid and myeloid populations in engrafted primary and secondary mice. These data document the cardinal stem cell features of self-renewal and multilineage differentiation of ESC-derived hematopoietic stem cells.

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Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells.

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