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Biology subjects

Lozito, T.

Publications and source records attributed to Lozito, T..

2 recordsLinked to original sources

Ilastik: a machine learning image analysis platform to interrogate stem cell fate decisions across multiple vertebrate species

Stem cells are the key cellular source for regenerating tissues and organs in vertebrate species. Historically, the investigation of stem cell fate decisions in vivo has been assessed in tissue sections using immunohistochemistry (IHC), where a trained user quantifies fluorescent signal in multiple randomly selected images using manual counting--which is prone to inaccuracies, bias, and is very labor intensive. Here, we highlight the performance of a recently developed machine-learning (ML)-based image analysis program called Ilastik using skeletal muscle as a model system. Interestingly, we demonstrate that Ilastik accurately quantifies Paired Box Protein 7 (PAX7)-positive muscle stem cells (MuSCs) before and during the regenerative process in whole muscle sections from mice, humans, axolotl salamanders, and short-lived African turquoise killifish, to a precision that exceeds human capabilities and in a fraction of the time. Overall, Ilastik is a free user-friendly ML-based program that will expedite the analysis of stained tissue sections in vertebrate animals.

cell biology↗

Signaling modality within gp130 receptor enhances tissue regeneration

Adult mammals are incapable of multi-tissue regeneration and augmentation of this potential may drastically shift current therapeutic paradigms. Here, we found that a common co-receptor of IL-6 cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) exhibit regenerative, not reparative, responses after wounding in skin and anti-degenerative responses in the synovial joint. In addition, pharmacological inhibition of gp130 Y814 results in regeneration of multiple tissues in several species as well as disease modification in animal models of osteoarthritis. Our study characterizes a novel molecular mechanism that, if selectively manipulated, enhances the intrinsic regenerative capacity while preventing pathological outcomes in injury and disease. SummaryGp130 Y814 signaling module serves as a cellular stress sensor responsible for hindering tissue regeneration while triggering pathological outcomes after injury.

molecular biology↗