Search

Epidermoid cysts are infrequent lesions occupying the intracranial space, comprising approximately 1–2% of all intracranial tumors. Brainstem epidermoids are exceptionally uncommon in children; up until now, only a few scattered case reports have been documented in the literature regarding this unique location. These cysts commonly arise from the inclusion of ectodermal elements during neural tube closure. Complete excision of these cysts is challenging due to their close proximity and adherence to the brainstem, which makes it difficult to achieve. As a result, recurrence of the cysts is not uncommon. We have reported a rare case of a 3-year-old with a 5-month history of progressive headache, imbalance while walking and progressive weakness in his right upper limb and lower limb along with difficulty in swallowing. On MRI Brain imaging study he had a pre-pontine epidermoid with intra-axial extension in the pons. The patient underwent retro-sigmoid/suboccipital craniotomy and microsurgical excision of the tumor, including the tumor capsule. After completing the surgery, the cavity was irrigated using a solution containing hydrocortisone and Ringer lactate to prevent the occurrence of aseptic meningitis. In the postoperative, the patient recovered without any complications, as all symptoms showed immediate improvement, and the lower cranial nerves returned to normal functioning. [ABSTRACT FROM AUTHOR]

Pluripotent embryonic stem cells (ESCs) can develop into any cell type in the body. Yet, the regulatory mechanisms that govern cell fate decisions during embryogenesis remain largely unknown. We now demonstrate that mouse ESCs (mESCs) display large natural variations in mitochondrial reactive oxygen species (mitoROS) levels that individualize their nuclear redox state, H3K4me3 landscape, and cell fate. While mESCs with high mitoROS levels (mitoROSHIGH) differentiate toward mesendoderm and form the primitive streak during gastrulation, mESCs, which generate less ROS, choose the alternative neuroectodermal fate. Temporal studies demonstrated that mesendodermal (ME) specification of mitoROSHIGH mESCs is mediated by a Nrf2-controlled switch in the nuclear redox state, triggered by the accumulation of redox-sensitive H3K4me3 marks, and executed by a hitherto unknown ROS-dependent activation process of the Wnt signaling pathway. In summary, our study explains how ESC heterogeneity is generated and used by individual cells to decide between distinct cellular fates. [Display omitted] • ESCs naturally differ in their mitochondrial ROS level • ESC fate decisions at the onset of gastrulation are governed by mitochondrial ROS • A high mitochondrial ROS level biases ESCs toward mesendodermal (ME) fates • ME specification is controlled by redox-sensitive ROS/p53-Wnt3/Nrf2-H3K4me3 axis How pluripotent embryonic stem cells (ESCs) choose distinct cell fates during embryonic development is still a mystery. Ulfig and Jakob now demonstrate that ESCs naturally differ in their mitochondrial reactive oxygen species levels that individualize their nuclear redox state, H3K4me3 landscape, and ultimately, cell fate. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, because cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but their functional consequences in differentiating cells are scarcely described. In this work, we show that the loss of chromosome 18q impairs neuroectoderm commitment and that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for this failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, and transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, suggesting that these cells are in an altered state of pluripotency., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Linking phenotypes to genetic components has been an essential part of novel drug discovery, and screening methods have been widely employed to achieve such a goal. Screens can be conducted in either pooled or arrayed formats. Although arrayed screenings provide a better and cheaper alternative in small scale, the larger-scale screenings are conducted in pooled manner. With its adaptability to various models and conditions, CRISPR/Cas9 technology provides an invaluable alternative to classical and RNAi-based screening methods. Combined with high-throughput sequencing and bioinformatics, CRISPR-/Cas9-based pooled screening methods provide unbiased and robust data. In this protocol, we employed CRISPR-/Cas9-based pooled screening for a non-binary and non-immediate readout., (© 2024. Springer Science+Business Media, LLC.)