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Cardiomyogenic differentiation is fine-tuned by differential mRNA association with polysomes.

ABSTRACT: BACKGROUND:Cardiac cell fate specification occurs through progressive steps, and its gene expression regulation features are still being defined. There has been an increasing interest in understanding the coordination between transcription and post-transcriptional regulation during the differentiation processes. Here, we took advantage of the polysome profiling technique to isolate and high-throughput sequence ribosome-free and polysome-bound RNAs during cardiomyogenesis. RESULTS:We showed that polysome-bound RNAs exhibit the cardiomyogenic commitment gene expression and that mesoderm-to-cardiac progenitor stages are strongly regulated. Additionally, we compared ribosome-free and polysome-bound RNAs and found that the post-transcriptional regulation vastly contributes to cardiac phenotype determination, including RNA recruitment to and dissociation from ribosomes. Moreover, we found that protein synthesis is decreased in cardiomyocytes compared to human embryonic stem-cells (hESCs), possibly due to the down-regulation of translation-related genes. CONCLUSIONS:Our data provided a powerful tool to investigate genes potentially controlled by post-transcriptional mechanisms during the cardiac differentiation of hESC. This work could prospect fundamental tools to develop new therapy and research approaches.

SUBMITTER: Pereira IT

PROVIDER: S-EPMC6420765 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Cardiomyogenic differentiation is fine-tuned by differential mRNA association with polysomes.

Pereira Isabela Tiemy IT Spangenberg Lucia L Robert Anny Waloski AW Amorín Rocío R Stimamiglio Marco Augusto MA Naya Hugo H Dallagiovanna Bruno B

BMC genomics 20190315 1

<h4>Background</h4>Cardiac cell fate specification occurs through progressive steps, and its gene expression regulation features are still being defined. There has been an increasing interest in understanding the coordination between transcription and post-transcriptional regulation during the differentiation processes. Here, we took advantage of the polysome profiling technique to isolate and high-throughput sequence ribosome-free and polysome-bound RNAs during cardiomyogenesis.<h4>Results</h4> ...[more]

PMID: 30876407

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Project description:A diversity of arthropods (myrmecophiles) thrives within ant nests, many of them unmolested though some, such as the specialized Eucharitidae parasitoids, may cause direct damage to their hosts. Ants are known to discriminate between nestmates and non-nestmates, but whether they recognize the strength of a threat and their capacity to adjust their behavior accordingly have not been fully explored. We aimed to determine whether Ectatomma tuberculatum ants exhibited specific behavioral responses to potential or actual intruders posing different threats to the host colony and to contribute to an understanding of complex ant-eucharitid interactions. Behavioral responses differed significantly according to intruder type. Ants evicted intruders that represented a threat to the colony's health (dead ants) or were not suitable as prey items (filter paper, eucharitid parasitoid wasps, non myrmecophilous adult weevils), but killed potential prey (weevil larvae, termites). The timing of detection was in accordance with the nature and size of the intruder: corpses (a potential source of contamination) were detected faster than any other intruder and transported to the refuse piles within 15 min. The structure and complexity of behavioral sequences differed among those intruders that were discarded. Workers not only recognized and discriminated between several distinct intruders but also adjusted their behavior to the type of intruder encountered. Our results confirm the previously documented recognition capabilities of E. tuberculatum workers and reveal a very fine-tuned intruder discrimination response. Colony-level prophylactic and hygienic behavioral responses through effective removal of inedible intruders appears to be the most general and flexible form of defense in ants against a diverse array of intruders. However, this generalized response to both potentially lethal and harmless intruders might have driven the evolution of ant-eucharitid interactions, opening a window for parasitoid attack and allowing adult parasitoid wasps to quickly leave the natal nest unharmed.

Project description:BackgroundHypoxia naturally happens in embryogenesis and thus serves as an important environmental factor affecting embryo development. Hif-1α, an essential hypoxia response factor, was mostly considered to mediate or synergistically regulate the effect of hypoxia on stem cells. However, the function and relationship of hypoxia and Hif-1α in regulating mesendoderm differentiation remains controversial.ResultsWe here discovered that hypoxia dramatically suppressed the mesendoderm differentiation and promoted the ectoderm differentiation of mouse embryonic stem cells (mESCs). However, hypoxia treatment after mesendoderm was established promoted the downstream differentiation of mesendoderm-derived lineages. These effects of hypoxia were mediated by the repression of the Wnt/β-Catenin pathway and the Wnt/β-Catenin pathway was at least partially regulated by the Akt/Gsk3β axis. Blocking the Wnt/β-Catenin pathway under normoxia using IWP2 mimicked the effects of hypoxia while activating the Wnt/β-Catenin pathway with CHIR99021 fully rescued the mesendoderm differentiation suppression caused by hypoxia. Unexpectedly, Hif-1α overexpression, in contrast to hypoxia, promoted mesendoderm differentiation and suppressed ectoderm differentiation. Knockdown of Hif-1α under normoxia and hypoxia both inhibited the mesendoderm differentiation. Moreover, hypoxia even suppressed the mesendoderm differentiation of Hif-1α knockdown mESCs, further implying that the effects of hypoxia on the mesendoderm differentiation were Hif-1α independent. Consistently, the Wnt/β-Catenin pathway was enhanced by Hif-1α overexpression and inhibited by Hif-1α knockdown. As shown by RNA-seq, unlike hypoxia, the effect of Hif-1α was relatively mild and selectively regulated part of hypoxia response genes, which fine-tuned the effect of hypoxia on mESC differentiation.ConclusionsThis study revealed that hypoxia is fine-tuned by Hif-1α and regulates the mesendoderm and ectoderm differentiation by manipulating the Wnt/β-Catenin pathway, which contributed to the understanding of hypoxia-mediated regulation of development.

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Cardiomyogenic differentiation is fine-tuned by differential mRNA association with polysomes.

Publications

Cardiomyogenic differentiation is fine-tuned by differential mRNA association with polysomes.

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