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FAM122A is required for mesendodermal and cardiac differentiation of embryonic stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE211341 | GEO | 2022/08/18

REPOSITORIES: GEO

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FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells.

Project description:Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved housekeeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multifaceted physiological and pathological processes. However, the in vivo function of FAM122A is largely unknown. In this study, we observed that Fam122 deletion resulted in embryonic lethality with severe defects of cardiovascular developments and significantly attenuated cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impaired mesendodermal specification and cardiac differentiation from mouse embryonic stem cells but showed no influence on pluripotent identity. Mechanical investigation revealed that the impaired differentiation potential was caused by the dysregulation of histone modification and Wnt and Hippo signaling pathways through modulation of PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This research not only significantly extends our understanding of the regulatory network of mesendodermal/cardiac differentiation but also proposes the potential significance of FAM122A in cardiac regeneration.

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FAM122A is required for mesendodermal and cardiac differentiation of embryonic stem cells [ChIP-seq]

Project description:Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved house-keeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multi facet physiological and pathological processes, however, the in vivo function of FAM122A is largely unknown. In this study, we found that Fam122 deletion results in embryonic lethality with severe defects of cardiovascular developments and significantly attenuates the cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impairs mesendodermal specification and cardiac differentiation from mouse embryonic stem cells, but not influences the pluripotent identity. Mechanical investigation shows that the impaired differentiation potential is caused through the dysregulation of histone modification and Wnt and Hippo signaling pathways by modulating PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This not only significantly extends our understanding the regulatory network of mesendodermal/cardiac differentiation, but also establishes a previously uncharacterized connection between PP2A and mesendodermal specification.

2022-08-18 | GSE211235 | GEO

FAM122A is required for mesendodermal and cardiac differentiation of embryonic stem cells [RNA-seq]

Project description:Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved house-keeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multi facet physiological and pathological processes, however, the in vivo function of FAM122A is largely unknown. In this study, we found that Fam122 deletion results in embryonic lethality with severe defects of cardiovascular developments and significantly attenuates the cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impairs mesendodermal specification and cardiac differentiation from mouse embryonic stem cells, but not influences the pluripotent identity. Mechanical investigation shows that the impaired differentiation potential is caused through the dysregulation of histone modification and Wnt and Hippo signaling pathways by modulating PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This not only significantly extends our understanding the regulatory network of mesendodermal/cardiac differentiation, but also establishes a previously uncharacterized connection between PP2A and mesendodermal specification.

2022-08-18 | GSE211234 | GEO

FAM122A is required for mesendodermal and cardiac differentiation of embryonic stem cells

Project description:FAM122A is required for mesendodermal and cardiac differentiation of embryonic stem cells

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CTCF acetylation at lysine 20 is required for early cardiac mesoderm differentiation from embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-24 | GSE181705 | GEO

ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-04-25 | GSE79701 | GEO

Reactive oxygen species enhance differentiation of human embryonic stem cells into mesendodermal lineage.

Project description:Recently, reactive oxygen species (ROS) have been studied as a regulator of differentiation into specific cell types in embryonic stem cells (ESCs). However, ROS role in human ESCs (hESCs) is unknown because mouse ESCs have been used mainly for most studies. Herein we suggest that ROS generation may play a critical role in differentiation of hESCs; ROS enhances differentiation of hESCs into bi-potent mesendodermal cell lineage via ROS-involved signaling pathways. In ROS-inducing conditions, expression of pluripotency markers (Oct4, Tra 1-60, Nanog, and Sox2) of hESCs was decreased, while expression of mesodermal and endodermal markers was increased. Moreover, these differentiation events of hESCs in ROS-inducing conditions were decreased by free radical scavenger treatment. hESC-derived embryoid bodies (EBs) also showed similar differentiation patterns by ROS induction. In ROS-related signaling pathway, some of the MAPKs family members in hESCs were also affected by ROS induction. p38 MAPK and AKT (protein kinases B, PKB) were inactivated significantly by buthionine sulfoximine (BSO) treatment. JNK and ERK phosphorylation levels were increased at early time of BSO treatment but not at late time point. Moreover, MAPKs family-specific inhibitors could prevent the mesendodermal differentiation of hESCs by ROS induction. Our results demonstrate that stemness and differentiation of hESCs can be regulated by environmental factors such as ROS.

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Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells.

Project description:The transcription factor BTB and CNC homology 1 (Bach1) is expressed in the embryos of mice, but whether Bach1 regulates the self-renewal and early differentiation of human embryonic stem cells (hESCs) is unknown. We report that the deubiquitinase ubiquitin-specific processing protease 7 (Usp7) is a direct target of Bach1, that Bach1 interacts with Nanog, Sox2, and Oct4, and that Bach1 facilitates their deubiquitination and stabilization via the recruitment of Usp7, thereby maintaining stem cell identity and self-renewal. Bach1 also interacts with polycomb repressive complex 2 (PRC2) and represses mesendodermal gene expression by recruiting PRC2 to the genes' promoters. The loss of Bach1 in hESCs promotes differentiation toward the mesendodermal germ layers by reducing the occupancy of EZH2 and H3K27me3 in mesendodermal gene promoters and by activating the Wnt/β-catenin and Nodal/Smad2/3 signaling pathways. Our study shows that Bach1 is a key determinant of pluripotency, self-renewal, and lineage specification in hESCs.

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Isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-05 | E-GEOD-74713 | biostudies-arrayexpress

FAM122A is required for hematopoietic stem cell function.

Project description: Not available

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