Molecular hallmarks of heterochronic parabiosis at single cell resolution

Molecular hallmarks of heterochronic parabiosis at single cell resolution. Palovics, R., Keller, A., Schaum, N., Tan, W., Fehlmann, T., Borja, M., Webber, J., McGeever, A., Bonanno, L., , undefined, Pisco, A. O., Karkanias, J., Neff, N. F., Darmanis, S., Quake, S. R., & Wyss-Coray, T. bioRxiv, Cold Spring Harbor Laboratory, 2020.

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Slowing or reversing biological ageing would have major implications for mitigating disease risk and maintaining vitality. While an increasing number of interventions show promise for rejuvenation, the effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. We performed single-cell RNA-sequencing on 13 organs to reveal cell type specific responses to young or aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, hematopoietic stem cells, hepatocytes, and endothelial cells from multiple tissues appear especially responsive. On the pathway level, young blood invokes novel gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. Intriguingly, we observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it. Altogether, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.Competing Interest StatementThe authors have declared no competing interest.

@article {Palovics2020.11.06.367078,
	author = {Palovics, Robert and Keller, Andreas and Schaum, Nicholas and Tan, Weilun and Fehlmann, Tobias and Borja, Michael and Webber, James and McGeever, Aaron and Bonanno, Liana and , and Pisco, Angela Oliveira and Karkanias, Jim and Neff, Norma F. and Darmanis, Spyros and Quake, Stephen R. and Wyss-Coray, Tony},
	title = {Molecular hallmarks of heterochronic parabiosis at single cell resolution},
	elocation-id = {2020.11.06.367078},
	year = {2020},
	doi = {10.1101/2020.11.06.367078},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Slowing or reversing biological ageing would have major implications for mitigating disease risk and maintaining vitality. While an increasing number of interventions show promise for rejuvenation, the effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. We performed single-cell RNA-sequencing on 13 organs to reveal cell type specific responses to young or aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, hematopoietic stem cells, hepatocytes, and endothelial cells from multiple tissues appear especially responsive. On the pathway level, young blood invokes novel gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. Intriguingly, we observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it. Altogether, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.Competing Interest StatementThe authors have declared no competing interest.},
	URL = {https://www.biorxiv.org/content/early/2020/11/08/2020.11.06.367078},
	eprint = {https://www.biorxiv.org/content/early/2020/11/08/2020.11.06.367078.full.pdf},
	journal = {bioRxiv}
}

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