Dataset Information

Temporal Impact of Substrate Anisotropy on Differentiating Cardiomyocyte Alignment and Functionality.

ABSTRACT: Anisotropic biomaterials can affect cell function by driving cell alignment, which is critical for cardiac engineered tissues. Recent work, however, has shown that pluripotent stem cell-derived cardiomyocytes may self-align over long periods of time. To determine how the degree of biomaterial substrate anisotropy impacts differentiating cardiomyocyte structure and function, we differentiated mouse embryonic stem cells to cardiomyocytes on nonaligned, semialigned, and aligned fibrous substrates and evaluated cell alignment, contractile displacement, and calcium transient synchronicity over time. Although cardiomyocyte gene expression was not affected by fiber alignment, we observed gradient- and threshold-based differences in cardiomyocyte alignment and function. Cardiomyocyte alignment increased with the degree of fiber alignment in a gradient-based manner at early time points and in a threshold-based manner at later time points. Calcium transient synchronization tightly followed cardiomyocyte alignment behavior, allowing highly anisotropic biomaterials to drive calcium transient synchronization within 8 days, while such synchronized cardiomyocyte behavior required 20 days of culture on nonaligned biomaterials. In contrast, cardiomyocyte contractile displacement had no directional preference on day 8 yet became anisotropic in the direction of fiber alignment on aligned fibers by day 20. Biomaterial anisotropy impact on differentiating cardiomyocyte structure and function is temporally dependent. Impact Statement This work demonstrates that biomaterial anisotropy can quickly drive desired pluripotent stem cell-derived cardiomyocyte structure and function. Such an understanding of matrix anisotropy's time-dependent influence on stem cell-derived cardiomyocyte function will have future applications in the development of cardiac cell therapies and in vitro cardiac tissues for drug testing. Furthermore, our work has broader implications concerning biomaterial anisotropy effects on other cell types in which function relies on alignment, such as myocytes and neurons.

SUBMITTER: Allen ACB

PROVIDER: S-EPMC6939589 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Temporal Impact of Substrate Anisotropy on Differentiating Cardiomyocyte Alignment and Functionality.

Allen Alicia C B ACB Barone Elissa E Momtahan Nima N Crosby Cody O CO Tu Chengyi C Deng Wei W Polansky Krista K Zoldan Janet J

Tissue engineering. Part A 20190820 19-20

Anisotropic biomaterials can affect cell function by driving cell alignment, which is critical for cardiac engineered tissues. Recent work, however, has shown that pluripotent stem cell-derived cardiomyocytes may self-align over long periods of time. To determine how the degree of biomaterial substrate anisotropy impacts differentiating cardiomyocyte structure and function, we differentiated mouse embryonic stem cells to cardiomyocytes on nonaligned, semialigned, and aligned fibrous substrates a ...[more]

PMID: 30727863

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Project description:BackgroundAccumulating evidence suggests that the human microbiome impacts individual and public health. City subway systems are human-dense environments, where passengers often exchange microbes. The MetaSUB project participants collected samples from subway surfaces in different cities and performed metagenomic sequencing. Previous studies focused on taxonomic composition of these microbiomes and no explicit functional analysis had been done till now.ResultsAs a part of the 2018 CAMDA challenge, we functionally profiled the available ~?400 subway metagenomes and built predictor for city origin. In cross-validation, our model reached 81% accuracy when only the top-ranked city assignment was considered and 95% accuracy if the second city was taken into account as well. Notably, this performance was only achievable if the similarity of distribution of cities in the training and testing sets was similar. To assure that our methods are applicable without such biased assumptions we balanced our training data to account for all represented cities equally well. After balancing, the performance of our method was slightly lower (76/94%, respectively, for one or two top ranked cities), but still consistently high. Here we attained an added benefit of independence of training set city representation. In testing, our unbalanced model thus reached (an over-estimated) performance of 90/97%, while our balanced model was at a more reliable 63/90% accuracy. While, by definition of our model, we were not able to predict the microbiome origins previously unseen, our balanced model correctly judged them to be NOT-from-training-cities over 80% of the time. Our function-based outlook on microbiomes also allowed us to note similarities between both regionally close and far-away cities. Curiously, we identified the depletion in mycobacterial functions as a signature of cities in New Zealand, while photosynthesis related functions fingerprinted New York, Porto and Tokyo.ConclusionsWe demonstrated the power of our high-speed function annotation method, mi-faser, by analysing ~?400 shotgun metagenomes in 2 days, with the results recapitulating functional signals of different city subway microbiomes. We also showed the importance of balanced data in avoiding over-estimated performance. Our results revealed similarities between both geographically close (Ofa and Ilorin) and distant (Boston and Porto, Lisbon and New York) city subway microbiomes. The photosynthesis related functional signatures of NYC were previously unseen in taxonomy studies, highlighting the strength of functional analysis.

Dataset Information

Temporal Impact of Substrate Anisotropy on Differentiating Cardiomyocyte Alignment and Functionality.

Publications

Temporal Impact of Substrate Anisotropy on Differentiating Cardiomyocyte Alignment and Functionality.

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