The role of histone deacetylases in embryonic development

Dsilva, Priyanka; Pai, Padmini; Shetty, Manasa Gangadhar; Shakuntala, K.

doi:10.1002/mrd.23659

Cited by 6 publications

(2 citation statements)

References 78 publications

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“…HDAC2 is a crucial member of the histone deacetylase family and is involved in the regulation of gene expression via epigenetic modifications. HDAC2 is also known to play a role in embryonic development and implantation ( Dsilva et al, 2023 ). Therefore we postulate that these transcription factors that govern ZNF81 gene regulation may also play a role in the embryo implantation process.…”

Section: Discussionmentioning

confidence: 99%

Do extracellular vesicles have specific target cells?; Extracellular vesicle mediated embryo maternal communication

Dissanayake,

Godakumara,

Muhandiram

et al. 2024

Front. Mol. Biosci.

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Extracellular vesicles (EVs) serve as messengers for intercellular communication, yet the precise mechanisms by which recipient cells interpret EV messages remain incompletely understood. In this study, we explored how the origin of EVs, their protein cargo, and the recipient cell type influence the cellular response to EVs within an embryo implantation model. We treated two types of EVs to 6 different recipient cell types and expression of zinc finger protein 81 (ZNF81) gene expression in the recipient cells were quantified using quantitative polymerase chain reaction (qPCR). The proteomic contents of the EV cargos were also analyzed. The results showed that downregulation of the ZNF81 gene was a specific cellular response of receptive endometrial epithelial cells to trophoblast derived EVs. Protein cargo analysis revealed that the proteomic profile of EVs depends on their cell of origin and therefore may affect the recipient cell response to EVs. Furthermore, trophoblastic EVs were found to be specifically enriched with transcription factors such as CTNNB1 (catenin beta-1), HDAC2 (histone deacetylase 2), and NOTCH1 (neurogenic locus notch homolog protein 1), which are known regulators of ZNF81 gene expression. The current study provided compelling evidence supporting the existence of EV specificity, where the characteristics of both the EVs and the recipient cell type collectively contribute to regulating EV target specificity. Additionally, EV protein cargo analysis suggested a potential association between transcription factors and the specific functionality of trophoblastic EVs. This in vitro embryo implantation model and ZNF81 read-out provides a unique platform to study EV specific functionality in natural cell-cell communication.

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Section: Discussionmentioning

confidence: 99%

Do extracellular vesicles have specific target cells?; Extracellular vesicle mediated embryo maternal communication

Dissanayake,

Godakumara,

Muhandiram

et al. 2024

Front. Mol. Biosci.

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“…Epigenetic modulators such as histone deacetylases (HDACs) are critical for early heart development as key regulators of regulating gene expresison 19, 20 . There are 18 known human HDACs, which can be subdivided into four classes based on their function and DNA sequence similarity.…”

Section: Introductionmentioning

confidence: 99%

Endocardial HDAC3 is required for myocardial trabeculation

Jang

Bentsen

Kim

et al. 2023

Preprint

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Background: Trabeculation, a key process in early heart development, is the formation of myocardial trabecular meshwork. The failure of trabeculation often leads to embryonic lethality. Support from endocardial cells, including the secretion of extracellular matrix (ECM) and growth factors is critical for trabeculation; however, it is unknown how the secretion of ECM and growth factors is initiated and regulated by endocardial cells. Methods: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of histone deacetylase 3 (HDAC3) in the developing endocardium. Results: We found that genetic deletion of Hdac3 in endocardial cells in mice resulted in early embryo lethality presenting as a hypotrabeculation cardiac phenotype. Single cell RNA sequencing identified several ECM components including collagens that were significantly downregulated in Hdac3 knockout (KO) endocardial cells. When cultured with supernatant from Hdac3 KO mouse cardiac endothelial cells (MCECs), wild-type mouse embryonic cardiomyocytes showed decreased proliferation, suggesting that growth signaling from Hdac3 KO MCECs is disrupted. Subsequent transcriptomic analysis revealed that transforming growth factor β3 (TGFβ3) was significantly downregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Mechanistically, we identified that microRNA (miR)-129-5p was significantly upregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Overexpression of miR-129-5p repressed Tgfβ3 expression in wild-type MCECs, whereas knockdown of miR-129-5p restored Tgfβ3 expression in Hdac3 KO MCECs. Conclusion: Our findings reveal a critical signaling pathway in which endocardial HDAC3 promotes trabecular myocardium growth by stimulating TGFβ signaling through repressing miR-129-5p, providing novel insights into the etiology of congenital heart disease and conceptual strategies to promote myocardial regeneration.

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