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Asymmetric division triggers cell-specific gene expression through coupled capture and stabilization of a phosphatase.

ABSTRACT: Formation of a division septum near a randomly chosen pole during sporulation in Bacillus subtilis creates unequal sized daughter cells with dissimilar programs of gene expression. An unanswered question is how polar septation activates a transcription factor (σ(F)) selectively in the small cell. We present evidence that the upstream regulator of σ(F), the phosphatase SpoIIE, is compartmentalized in the small cell by transfer from the polar septum to the adjacent cell pole where SpoIIE is protected from proteolysis and activated. Polar recognition, protection from proteolysis, and stimulation of phosphatase activity are linked to oligomerization of SpoIIE. This mechanism for initiating cell-specific gene expression is independent of additional sporulation proteins; vegetative cells engineered to divide near a pole sequester SpoIIE and activate σ(F) in small cells. Thus, a simple model explains how SpoIIE responds to a stochastically-generated cue to activate σ(F) at the right time and in the right place.

SUBMITTER: Bradshaw N

PROVIDER: S-EPMC4714977 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Restriction on self-renewing asymmetric division is coupled to terminal asymmetric division in the Drosophila CNS.

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Bistability of a coupled Aurora B kinase-phosphatase system in cell division.

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Mechanical stretch triggers rapid epithelial cell division through Piezo1.

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Cell type-specific attenuation of brassinosteroid signaling precedes stomatal asymmetric cell division

Project description:In Arabidopsis thaliana, brassinosteroid (BR) signaling and stomatal development are connected through the SHAGGY/GSK3-like kinase BR INSENSITIVE2 (BIN2). BIN2 is a key negative regulator of BR signaling but it plays a dual role in stomatal development. BIN2 promotes or restricts stomatal asymmetric cell division (ACD) depending on its subcellular localization, which is regulated by the stomatal lineage-specific scaffold protein POLAR. BRs inactivate BIN2, but how they govern stomatal development remains unclear. Mapping the single-cell transcriptome of stomatal lineages after triggering BR signaling with either exogenous BRs or the specific BIN2 inhibitor, bikinin, revealed that the two modes of BR signaling activation generate spatiotemporally distinct transcriptional responses. We established that BIN2 is always sensitive to the inhibitor but, when in a complex with POLAR and its closest homolog POLAR-LIKE1, it becomes protected from BR-mediated inactivation. Subsequently, BR signaling in ACD precursors is attenuated, while it remains active in epidermal cells devoid of scaffolds and undergoing differentiation. Our study demonstrates how scaffold proteins contribute to cellular signal specificity of hormonal responses in plants.

2023-08-30 | GSE193451 | GEO

Islr regulates satellite cells asymmetric division through Sparc/p-ERK1/2 signaling pathway

Project description:Satellite cells are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The balance between stem cell self-renewal and differentiation impacts the kinetics and efficiency of skeletal muscle regeneration. This study elucidated the function of Islr in satellite cell asymmetric division. Satellite cell specific deletion of Islr compromises muscle regeneration in adult mice by impairing the satellite cell pool. Islr is pivotal for satellite cell proliferation and its deletion promotes asymmetric cell fate segregation of satellite cells. A mechanistic search revealed that Islr interacts and stabilizes the Sparc protein, which activates p-ERK1/2 signaling required for asymmetric division. In combination, the findings have identified Islr as a key regulator of satellite cell asymmetric division through the Sparc/p-ERK1/2 signaling pathway, which provides a new insight into satellite cell biology and open avenues for the treatment of myopathy.

2023-08-16 | GSE210951 | GEO

Haspin regulates mouse embryonic stem cell developmental potencies through Wnt5a mediated asymmetric cell division

Project description:To investigate the function of Haspin in the mouse embryonic stem cell, we established Haspin knockout cell lines.

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Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division.

Project description:Dystrophin is expressed in differentiated myofibers, in which it is required for sarcolemmal integrity, and loss-of-function mutations in the gene that encodes it result in Duchenne muscular dystrophy (DMD), a disease characterized by progressive and severe skeletal muscle degeneration. Here we found that dystrophin is also highly expressed in activated muscle stem cells (also known as satellite cells), in which it associates with the serine-threonine kinase Mark2 (also known as Par1b), an important regulator of cell polarity. In the absence of dystrophin, expression of Mark2 protein is downregulated, resulting in the inability to localize the cell polarity regulator Pard3 to the opposite side of the cell. Consequently, the number of asymmetric divisions is strikingly reduced in dystrophin-deficient satellite cells, which also display a loss of polarity, abnormal division patterns (including centrosome amplification), impaired mitotic spindle orientation and prolonged cell divisions. Altogether, these intrinsic defects strongly reduce the generation of myogenic progenitors that are needed for proper muscle regeneration. Therefore, we conclude that dystrophin has an essential role in the regulation of satellite cell polarity and asymmetric division. Our findings indicate that muscle wasting in DMD not only is caused by myofiber fragility, but also is exacerbated by impaired regeneration owing to intrinsic satellite cell dysfunction.

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Gene expression of CD8 T cell progenies generated via asymmetric cell division

Project description:Asymmetric partitioning of fate-determinants is a mechanism that contributes to T cell differentiation. However, it remained unclear whether the ability of T cells to divide asymmetrically is influenced by their differentiation state, as well as if enforcing asymmetric cell division rates would have an impact on T cell differentiation and memory formation. Using the murine LCMV infection model, we established a correlation between cell stemness and the ability of CD8+ T cells to undergo asymmetric cell division (ACD). Transient mTOR inhibition proved to increase ACD rates in naïve and memory cells, and to install this ability in exhausted CD8+ T cells. Functionally, enforced ACD correlated with increased memory potential, leading to more efficient recall response and viral control upon acute or chronic LCMV infection. Moreover, transient mTOR inhibition also increased ACD rates in human CD8+ T cells. Transcriptional profiling of first daughter cells, obtained by sorting CD8lo and CD8hi cells after in vitro stimulation, revealed that progenies emerging from enforced ACD exhibited more pronounced early memory signatures, which functionally endowed these cells with strengthened memory features.

2019-02-14 | E-MTAB-7651 | biostudies-arrayexpress

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