Lin28

Pediatric brain tumors currently show the highest incidence among solid childhood malignancies and, together with leukemia, are the leading cause of death from cancer in childhood. Embryonal brain tumors are the most common and frequent type of childhood brain cancer and are usually characterized by an extremely aggressive course of the disease with the worst outcomes in most cases. There is an urgent need for specific refined molecular diagnostics, which would help to develop personalized treatment. In the present review paper, the latest molecular characteristics of various classified forms of embryonal brain tumors were analyzed in detail...

Busulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self-renewal and differentiation. It has been demonstrated that the omega-3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega-3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography...

BACKGROUND: Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling. METHODS: hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation...

Diamond-Blackfan anemia (DBA) is a congenital hypoplastic anemia characterized by ineffective erythropoiesis. DBA is majorly caused by mutations in the ribosomal protein (RP) genes (Gadhiya and Wills in Diamond-Blackfan Anemia, https://www.statpearls.com/ ; 2023). A suitable disease model that yields a continuous supply of erythroid cells is required to study disease pathogenesis and drug discovery. Toward this, we reprogrammed dermal fibroblasts from a DBA patient with a heterozygous mutation c.22-23delAG in the RPS19 gene identified through exome sequencing...

BACKGROUND: Zinc (Zn) is the second most abundant trace element after Fe, present in the human body. It is frequently reported in association with cell growth and proliferation, and its deficiency is considered to be a major disease contributing factor. AIM: To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord (hUC)-derived mesenchymal stem cells (MSCs). METHODS: hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry, immunophenotyping, and tri-lineage differentiation...

The highly conserved RNA-binding protein LIN28B and focal adhesion kinase (FAK) are significantly upregulated in ovarian cancer (OC), serving as markers for disease progression and prognosis. Nonetheless, the correlation between LIN28B and FAK, as well as the pharmacological effects of the LIN28 inhibitor C1632, in OC cells have not been elucidated. The present study demonstrates that C1632 significantly reduced the rate of DNA replication, arrested the cell cycle at the G0/G1 phase, consequently reducing cell viability, and impeding clone formation...

In the last four decades, advances in assisted reproductive technology (ART) have offered hope to individuals with fertility problems to conceive. However, a closer examination of the clinical outcomes of ART shows a stark contrast in Asian women compared to Caucasians, with majority of studies reporting lower reproductive success among Asian women. We performed a systematic review to elucidate the genes associated with ART clinical outcomes, with a focus on Asian ethnicities. We completed a database search to identify all studies associated with reproductive outcomes in women of different ethnic backgrounds...

The emergence and development of induced pluripotent stem cells (iPSCs) provides an approach to understand the regulatory mechanisms of cell pluripotency and demonstrates the great potential of iPSCs in disease modeling. Acute myelitis defines a group of inflammatory diseases that cause acute nerve damage in the spinal cord; however, its pathophysiology remains to be elusive. In this study, we derived skin fibroblasts from a patient with acute myelitis (P-HAF) and then reprogrammed P-HAF cells to iPSCs using eight exogenous factors (namely, OCT4, SOX2, c-MYC, KLF4, NANOG, LIN28, RARG, and LRH1 )...

SIX2-positive urine derived renal progenitor cells were isolated from a male and female alpha1-antitrypsin deficiency (AATD) patients both harboring the homozygous PiZZ genotype. The cells were reprogrammed to generate two integration-free induced pluripotent stem cell (iPSC) lines by transfecting episomal-based plasmids expressing OCT4, SOX2, NANOG, c-MYC, KLF4 and LIN28. Pluripotency was confirmed by immunocytochemistry for associated markers and embryoid body-based differentiation into the three germ layers...

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Understanding the mechanism of stem cell maintenance underlies the establishment of long-term and mass culture methods for stem cells that are fundamental for clinical and agricultural applications. In this study, we use chicken primordial germ cell (PGC) as a model to elucidate the molecular mechanisms underlying stem cell maintenance. The PGC is a useful experimental model because it is readily gene-manipulatable and easy to test gene function in vivo using transplantation. Previous studies to establish a long-term culture system have shown that secreted factors such as FGF2 are required to maintain the self-renewal capability of PGC...

BACKGROUND: A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. METHODS: Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells...

Expanded human lymphoblast cells from three different aged healthy individuals, 8-year-old male, 0-year-old newborn (NB) male, and 26-year-old female, were used to generate induced pluripotent stem cell (iPSC) lines TRNDi033-A, TRNDi034-A and TRNDi035-A, respectively, by exogenous expression of five reprogramming factors, human OCT4, SOX2, KLF4, L-MYC and LIN28. The authenticity of established iPSC lines was confirmed by the expressions of stem cell markers, karyotype analysis, embryoid body formation, and scorecard analysis...

Adult human primary dermal fibroblasts [ATCC (PCS-201-012)] were reprogrammed by transfection of oriP/EBNA-1 based episomal plasmids expressing OCT3/4, SOX2, KLF4, L-MYC, LIN28 and a p53 shRNA (Okita et al., 2011) to give rise to induced pluripotent stem cells (iPSCs). These iPSCs expressed core pluripotency markers, maintained normal karyotype, and showed tri-lineage differentiation potential. Further, the absence of episomal plasmid integration in this iPSC line was confirmed by genomic PCR. In addition, DNA fingerprinting of fibroblast and iPSC DNA by microsatellite analysis confirmed the genetic identity of this cell line...

Children with group 3 medulloblastoma (G3 MB) have a very poor prognosis and many do not survive beyond 5 years after diagnosis. A factor that may contribute to this is the lack of available targeted therapy. Expression of protein lin-28 homolog B (LIN28B), a regulator of developmental timing, is upregulated in several cancers, including G3 MB, and is associated with worse survival in this disease. Here, we investigate the role of the LIN28B pathway in G3 MB and demonstrate that the LIN28B-lethal-7 (let-7; a microRNA that is a tumor suppressor)-lymphokine-activated killer T-cell-originated protein kinase (PBK; also known as PDZ-binding kinase) axis promotes G3 MB proliferation...

The identification of small molecules capable of replacing transcription factors has been a longstanding challenge in the generation of human chemically induced pluripotent stem cells (iPSCs). Recent studies have shown that ectopic expression of OCT4, one of the master pluripotency regulators, compromised the developmental potential of resulting iPSCs, This highlights the importance of finding endogenous OCT4 inducers for the generation of clinical-grade human iPSCs. Through a cell-based high throughput screen, we have discovered several new OCT4-inducing compounds (O4Is)...

Let-7 miRNAs have pleiotropic cellular functions in cell proliferation, migration, and regenerative processes. Here, we investigate whether the inhibition of let-7 miRNAs with antisense oligonucleotides (ASOs) can be a transient and safe strategy enhancing the therapeutic potential of mesenchymal stromal cells (MSCs) to overcome their limitations in cell therapeutic trials. We first identified major subfamilies of let-7 miRNAs preferentially expressed in MSCs, and efficient ASO combinations against these selected subfamilies that mimic the effects of LIN28 activation...

Targeting the protein-RNA interaction of LIN28 and let-7 is a promising strategy for the development of novel anticancer therapeutics. However, a limited number of small-molecule inhibitors disrupting the LIN28-let-7 interaction with potent efficacy are available. Herein, we developed a novel LIN28-inhibiting strategy by targeting selective hotspot amino acids at the LIN28-let-7 binding interface with small-molecule-based bifunctional conjugates. Starting from reported small-molecule LIN28 inhibitors, we identified a feasible linker-attachment position after performing a structure-activity relationship exploration based on LIN28-targeting chromenopyrazoles...

Transdifferentiation of type II alveolar cells (AECII) is a major cause for radiation-induced lung fibrosis (RILF). Cell differentiation phenotype is determined by Lin28 (undifferentiated marker) and let-7 (differentiated marker) in a see-saw-pattern. Therefore, differentiation phenotype can be extrapolated based on Lin28/let-7 ratio. Lin28 is activated by β-catenin. To the best of our knowledge this study was the first to use the single primary AECII freshly isolated from irradiated lungs of fibrosis-resistant C3H/HeNHsd strain to further confirm RILF mechanism by comparing its differences in AECII phenotype status/state and cell differentiation regulators to fibrosis-prone C57BL/6j mice...

Small-molecule inhibitors of the RNA-binding and regulating protein LIN28 have the potential to be developed as chemical probes for biological perturbation and as therapeutic candidates. Reported small molecules disrupting the interaction between LIN28 and let-7 miRNA suffer from moderate to weak inhibitory activity and flat structure-activity relationship, which hindered the development of next-generation LIN28 inhibitors that warrant further evaluations. We report herein the identification of new LIN28 inhibitors utilizing a spirocyclization strategy based on a chromenopyrazole scaffold...