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https://www.science.org/doi/10.1126/science.abn3100

There are few studies on the functions of the Y chromosome beyond sex determination, although previous studies have found that men lose the Y chromosome as they age white blood cells , UK Biobank 70 Approximately 40% of age-old men will have partial loss of chromosome Y (mLOY) found in white blood cells, but it is not clear whether this causes disease (1, 2).

To this end, University of Virginia Kenneth Walsh and other researchers used in vitro gene editing + "bone marrow transplantation" method to create mice in which some white blood cells lack the Y chromosome (mLOY mice ; about 49% to 81% of the white blood cells lack the Y chromosome chromosome), it was found that the life span of these mice was shortened and the degree of organ fibrosis increased; if the heart failure model is further constructed (surgery is performed to narrow the key aorta and increase the burden on the heart) it will further aggravate cardiac fibrosis in mLOY mice, etc. Phenotype(2).

mLOY mice have shorter lifespan and increased organ fibrosis (A); heart failure model (TAC surgery) further aggravates cardiac fibrosis (B) (2)

further analyzed its mechanism, and the researchers found that macrophages in mLOY mice promotes fibrosis and the signal is active. If the neutralizing antibody is used to block the key cytokine-TGFβ that promotes fibrosis, phenotypes such as cardiac fibrosis in mLOY mice can be reversed (2).

Blocking TGFβ with antibodies can alleviate cardiac fibrosis in the heart failure model mLOY mice (2)

This work was published in Science on July 14, 2022; the researchers said that an important practical significance of this study is to suggest that some leukocytes Y Heart disease patients with chromosomal loss are potentially more likely to benefit from antifibrotic treatments (2).

Comment(s):

The phenotype is very clear; but the more in-depth mechanism, such as what other tissues or cells besides white blood cells have Y chromosome loss? Why is it lost? How is the pro-fibrotic signaling network activated after loss? Waiting for further analysis.

Corresponding author introduction:

https://med.virginia.edu/faculty/faculty-listing/kw9ar/

References:

1. D. J. Thompson et al., Genetic predisposition to mosaic Y chromosome loss in blood. Nature 575, 652 –657 (2019).

2. S. Sano et al., Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality. Science (80-. ). 377, 292–297 (2022).

Original link:

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