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Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions [ClariomS]

ABSTRACT: Hippo kinases Mst1 and Mst2 act as molecular rheostats for the terminal maturation and effector differentiation programs of iNKT cells. Loss of Mst1 alone or with Mst2 impedes iNKT cell development, associated with defective IL-15-dependent cell survival

ORGANISM(S): Mus musculus

PROVIDER: GSE144776 | GEO | 2020/04/18

REPOSITORIES: GEO

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Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions [MoGene-2_0]

Project description:Hippo kinases Mst1 and Mst2 act as molecular rheostats for the terminal maturation and effector differentiation programs of iNKT cells. iNKT developmental stages 1, 2, and 3 (S1, S2, S3) were sorted from the thymus of WT (n = 3) and Cd4CreMst1fl/fl (n = 3) mice

2020-04-07 | GSE130043 | GEO

Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions.

Project description:Invariant natural killer T (iNKT) cells acquire effector functions during development by mechanisms that remain poorly understood. Here, we show that the Hippo kinases Mst1 and Mst2 act as molecular rheostats for the terminal maturation and effector differentiation programs of iNKT cells. Loss of Mst1 alone or together with Mst2 impedes iNKT cell development, associated with defective IL-15-dependent cell survival. Mechanistically, Mst1 enforces iNKT cellular and transcriptional quiescence associated with maturation and commitment to iNKT1 cells by suppressing proliferation and Opa1-related mitochondrial metabolism that are dynamically regulated during iNKT cell development. Furthermore, Mst1 shapes the reciprocal fate decisions between iNKT1 and iNKT17 effector cells, which respectively depend upon mitochondrial dynamics and ICOS-mTORC2 signaling. Collectively, these findings establish Mst1 as a crucial regulator of mitochondrial homeostasis and quiescence in iNKT cell development and effector lineage differentiation and highlight that establishment of quiescence programs underlies iNKT cell development and effector maturation.

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Hippo kinases Mst1 and Mst2 sense and amplify IL-2R−STAT5 signaling in Treg cells to establish stable regulatory activity

Project description:Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Tregs can respond to low levels of IL-2, but the mechanisms by which STAT5 is activated during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2−STAT5 activity in Tregs. Tregs had high Mst1 and Mst2 (Mst1−Mst2) activity that was crucial to prevent tumor resistance and autoimmunity. Mechanistically, Mst1−Mst2 sensed IL-2 signals to promote the STAT5 activation necessary for Treg cell homeostasis and lineage stability, and maintain the highly suppressive phophorylated-STAT5+ Treg cell subpopulation. Unbiased quantitative proteomics revealed an association of Mst1 with the cytoskeletal DOCK8−LRCHs module that shaped activity Rho-family GTPase Rac activity, which in turn mediated STAT5 activation in Tregs. Collectively, IL-2−STAT5 signaling critically depends upon Mst1−Mst2 functions to maintain a stable Treg cell pool and immune tolerance. We used microarrays to compare the global transcription profiles of WT and Mst1/Mst2-null Treg cell populations

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Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions

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

2020-04-07 | GSE144778 | GEO

Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions

Project description:Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions

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Expression data from Mst knockout embryoid bodies and wild type embryoid bodies

Project description:Mst1/Mst2 are central components of Hippo pathway. We examined the role of Mst1/Mst2 in ES cell differentiation. In this data set, we include expression data from day 4 and day 8 Mst1/Mst2 knockout ES cell formed embryoid bodies and wild type embryoid body controls. total 4 samples.

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Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions [ClariomS]

Project description:Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions [ClariomS]

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Microarray of Mst1/2 deleted epithelial cells from E18.5 mouse lungs

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RNA-seq analysis of Mst1/2 deleted bronchiolar epithelial cells from adult mouse lungs

Project description:Mst1 and Mst2 were conditionally deleted from non-ciliated bronchiolar epithelial cells in the mature lung. Bronchiolar epithelial cells from control and Mst1/2 deleted mice were isolated by cell sorting and used for RNA-seq analysis. Scgb1a1-rtTA/tetO-Cre/Mst1;2-flx/flx (Mst1/2 D/D) mice were generated to conditionally delete Mst1 and Mst2 from non-ciliated, secretory bronchiolar epithelial cells. Adult mice were maintained on doxycycline food for 16 days to induce deletion of Mst1/2. Lin-/CD326+/CD24-intermediate cells were isolated by fluorescence cell sorting to enrich for the targeted airway epithelial cells. mRNA isolated from Lin-/CD326+/CD24-intermediate cells from control and Mst1/2 D/D mice was pooled and analyzed by RNA-seq to identify transcriptional changes following deletion of Mst1 and Mst2 from mature lung bronchiolar epithelial cells.

2015-01-01 | E-GEOD-61627 | biostudies-arrayexpress

Expression data from Mst knockout embryoid bodies and wild type embryoid bodies

2014-01-02 | GSE50219 | GEO