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Macrophage-Secreted CSF1 Transmits a Calorie Restriction-Induced Self-Renewal Signal to Mammary Epithelial Stem Cells
Year:
2022
Source of publication :
Cells
Authors :
Barash, Itamar
;
.
Volume :
Co-Authors:

Anna Kosenko 
Tomer Meir Salame
Gilgi Friedlander
Itamar Barash

Facilitators :
From page:
0
To page:
0
(
Total pages:
1
)
Abstract:

Calorie restriction enhances stem cell self-renewal in various tissues, including the mammary gland. We hypothesized that similar to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in energy supply, depending instead on niche signaling. The latter was investigated by subjecting cultures of mammary epithelial stem cells for 8 days to in vivo paracrine calorie-restriction signals collected from a 4-day-conditioned medium of individual mammary cell populations. Conditioned medium from calorie-restricted non-epithelial cells induced latent cell propagation and mammosphere formation-established markers of stem cell self-renewal. Combined RNA-Seq, immunohistochemistry and immunofluorescence analyses of the non-epithelial population identified macrophages and secreted CSF1 as the energy sensor and paracrine signal, respectively. Calorie restriction-induced pStat6 expression in macrophages suggested that skewing to the M2 phenotype contributes to the sensing mechanism. Enhancing CSF1 signaling with recombinant protein and interrupting the interaction with its highly expressed receptor in the epithelial stem cells by neutralizing antibodies were both affected stem cell self-renewal. In conclusion, combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the calorie restriction-induced effect on mammary stem cell self-renewal.

Note:
Related Files :
Calorie restriction
CSF1
macrophage
Mammary gland
monocyte
niche
RNA sequencing
Stem cell
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More details
DOI :
10.3390/cells11182923
Article number:
0
Affiliations:
Database:
PubMed
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
62331
Last updated date:
03/10/2022 18:41
Creation date:
03/10/2022 18:41
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Scientific Publication
Macrophage-Secreted CSF1 Transmits a Calorie Restriction-Induced Self-Renewal Signal to Mammary Epithelial Stem Cells

Anna Kosenko 
Tomer Meir Salame
Gilgi Friedlander
Itamar Barash

Macrophage-Secreted CSF1 Transmits a Calorie Restriction-Induced Self-Renewal Signal to Mammary Epithelial Stem Cells

Calorie restriction enhances stem cell self-renewal in various tissues, including the mammary gland. We hypothesized that similar to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in energy supply, depending instead on niche signaling. The latter was investigated by subjecting cultures of mammary epithelial stem cells for 8 days to in vivo paracrine calorie-restriction signals collected from a 4-day-conditioned medium of individual mammary cell populations. Conditioned medium from calorie-restricted non-epithelial cells induced latent cell propagation and mammosphere formation-established markers of stem cell self-renewal. Combined RNA-Seq, immunohistochemistry and immunofluorescence analyses of the non-epithelial population identified macrophages and secreted CSF1 as the energy sensor and paracrine signal, respectively. Calorie restriction-induced pStat6 expression in macrophages suggested that skewing to the M2 phenotype contributes to the sensing mechanism. Enhancing CSF1 signaling with recombinant protein and interrupting the interaction with its highly expressed receptor in the epithelial stem cells by neutralizing antibodies were both affected stem cell self-renewal. In conclusion, combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the calorie restriction-induced effect on mammary stem cell self-renewal.

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