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Application of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis.
Abstract
Studies of heterochronic parabiosis demonstrated that with age, the composition of the circulatory milieu changes in ways that broadly inhibit tissue regenerative capacity. In addition, local tissue niches have age-specific influences on their resident stem cells. Here we use bio-orthogonal proteome labeling for detecting in vivo proteins present only in transplanted myoblasts, but not in host tissue, and proteins exclusive to one young mouse and transferred during parabiosis to its old partner. We use a transgenic mouse strain that ubiquitously expresses a modified tRNA methionine synthase, metRS, which preferentially incorporates the methionine surrogate azido-nor-leucine (ANL) into newly generated proteins. Using click chemistry and a modified antibody array to detect ANL-labeled proteins, we identify several ‘young’ systemic factors in old regenerating muscle of the heterochronic parabiotic partners. Our approach enables the selective profiling of mammalian proteomes in mixed biological environments such as cell and tissue transplantation, apheresis or parabiosis.
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In the power simulation, when variance of independent experiments is low and difference in effect size between cohorts is high, there is no difference in Power between N=4, 8, 19, or infinity.
“As shown in Figure 1, when the Variance of independent experiments is low and the difference in ES between the cohorts is high, e.g. as in our 2003-2020, including published and current studies on young, old and rejuvenated old cohorts [1–3, 4, 9] there is no difference in Power between N=4, 8, 19, or infinity.”
From Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin (2020) · cites this paper as [2]
The Results section describes a study comparing young and old mice in heterochronic parabiosis, so the paper supports its use as an example of work involving those cohorts. The Methods section reports experimental sample sizes and statistical tests, but neither it nor the retrieved passages report a power simulation or show equal power at N=4, 8, 19, and infinity. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOld human serum strongly reduced myogenic cell proliferation.
“As demonstrated in Figure 2, old human serum strongly reduced myogenic cell proliferation (which is consistent with the effects of the old mouse serum [1, 2, 6, 7, 13]).”
From Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin (2020) · cites this paper as [2]
The citation is attached to the parenthetical comparison with old mouse serum; the old-human-serum result is presented as the citing authors’ own Figure 2 finding. The source paper’s Introduction (page unavailable) discusses potentially inhibitory old-blood molecules, and its Results discuss age-related inhibition of muscle repair, but neither passage reports that old human serum strongly reduced myogenic cell proliferation. Searches for old human serum and serum effects on myogenic proliferation found no such result. (LLM, conf=0.78)
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Rejuvenation of aged progenitor cells by exposure to a young systemic environment
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Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats
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Age dependent increase in the levels of osteopontin inhibits skeletal muscle regeneration
Paliwal, P., Pishesha, N., Wijaya, D., & Conboy, I. M. (2012) · Aging · doi:10.18632/aging.100477 · Cited by 89
Self-citationRole of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging
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Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin
Mehdipour, M., Skinner, C., Wong, N., Lieb, M., Liu, C., Etienne, J., Kato, C., Kiprov, D., Conboy, M. J., & Conboy, I. M. (2020) · Aging · doi:10.18632/aging.103418 · Cited by 115
Self-citationCell-type-specific metabolic labeling, detection and identification of nascent proteomes in vivo
Alvarez-Castelao, B., Schanzenbächer, C. T., Langer, J. D., & Schuman, E. M. (2019) · Nature Protocols · doi:10.1038/s41596-018-0106-6 · Cited by 84
Metadata
- Authors
- Liu, Y., Conboy, M. J., Mehdipour, M., Liu, Y., Tran, T. P., Blotnick, A., Rajan, P., Santos, T. C., & Conboy, I. M.
- ORCID
- Liu, Yutong
- Venue
- Nature Communications
- Published
- 2017-09-21
- Volume
- 8
- Issue
- 1
- ISSN
- 2041-1723
- PMC
- PMC5608760
- Cited by
- 59
- References
- 11
- Language
- en
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