stem cells

Novel PROTAC probes targeting KDM3 degradation to eliminate colorectal cancer stem cells through inhibition of Wnt/β-catenin signaling

RSC Med. Chem., 2024, 15,3746-3758
DOI: 10.1039/D4MD00122B, Research Article
Open Access
Shadid U. Zaman, Piyusha P. Pagare, Hongguang Ma, Rosalie G. Hoyle, Yan Zhang, Jiong Li
We designed and synthesized novel IOX1-based PROTACs, which can selectively degrade KDM3A and KDM3B to eliminate colorectal cancer stem cells through inhibition of Wnt signaling.
The content of this RSS Feed (c) The Royal Society of Chemistry




stem cells

Role of Stem Cells in Bone Marrow Transplantation

The science behind stem cells in bone marrow transplantation, how it revolutionizes cancer treatment and how it holds the potential to transform lives, offering renewed hope and vitality to patients battling cancer.




stem cells

How Stem Cells Stay Young

Bone marrow stem cells defy typical aging, and it may be because they express the right proteins.



  • News
  • News & Opinion

stem cells

Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness [Molecular Biophysics]

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.




stem cells

AMPK{beta}1 and AMPK{beta}2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification [Cell Biology]

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.




stem cells

Therapeutic targeting of pancreatic cancer stem cells by dexamethasone modulation of the MKP-1-JNK axis [Cell Biology]

Postoperative recurrence from microscopic residual disease must be prevented to cure intractable cancers, including pancreatic cancer. Key to this goal is the elimination of cancer stem cells (CSCs) endowed with tumor-initiating capacity and drug resistance. However, current therapeutic strategies capable of accomplishing this are insufficient. Using in vitro models of CSCs and in vivo models of tumor initiation in which CSCs give rise to xenograft tumors, we show that dexamethasone induces expression of MKP-1, a MAPK phosphatase, via glucocorticoid receptor activation, thereby inactivating JNK, which is required for self-renewal and tumor initiation by pancreatic CSCs as well as for their expression of survivin, an anti-apoptotic protein implicated in multidrug resistance. We also demonstrate that systemic administration of clinically relevant doses of dexamethasone together with gemcitabine prevents tumor formation by CSCs in a pancreatic cancer xenograft model. Our study thus provides preclinical evidence for the efficacy of dexamethasone as an adjuvant therapy to prevent postoperative recurrence in patients with pancreatic cancer.




stem cells

Scientists Create Fertile Ground for Growing Stem Cells

Title: Scientists Create Fertile Ground for Growing Stem Cells
Category: Health News
Created: 8/23/2010 10:10:00 AM
Last Editorial Review: 8/24/2010 12:00:00 AM




stem cells

Scientists Grow 'Model Brain' From Stem Cells

Title: Scientists Grow 'Model Brain' From Stem Cells
Category: Health News
Created: 8/28/2013 2:35:00 PM
Last Editorial Review: 8/29/2013 12:00:00 AM




stem cells

Mouse Study Suggests Stem Cells May Reverse Stroke Damage

Title: Mouse Study Suggests Stem Cells May Reverse Stroke Damage
Category: Health News
Created: 8/22/2016 12:00:00 AM
Last Editorial Review: 8/23/2016 12:00:00 AM




stem cells

Lab-grown stem cells could be a 'breakthrough' for cancer treatment

Stem cells made in the lab may one day aid cancer treatment by reducing our reliance on donors




stem cells

Kennedy's FDA Wish List: Raw Milk, Stem Cells, Heavy Metals...


Kennedy's FDA Wish List: Raw Milk, Stem Cells, Heavy Metals...


(First column, 9th story, link)


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stem cells

Scientists Uncover Stem Cells in the Thymus for the First Time

For the first time, scientists at the Francis Crick Institute have pinpointed medlinkstem cells/medlink within the human thymus, offering a fresh




stem cells

Blood Stem Cells: Key to Immune Aging and Longevity

Blood stem cells contribute to maintaining the age-related imbalance of the two main types of immune cells innate and adaptive. Effective immune systems




stem cells

Mechanical guidance to self-organization and pattern formation of stem cells

Soft Matter, 2024, Advance Article
DOI: 10.1039/D4SM00172A, Paper
Wei-Hua Zhou, Lin-Ru Qiao, She-Juan Xie, Zhuo Chang, Xu Yin, Guang-Kui Xu
We introduce a mechanical model based on the dynamic balance between cell-ECM-culture environment, and demonstrate that it can capture specific phenomena in stem cell pattern formation experiments guided by geometric constraints.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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stem cells

Stem cells hold new hope for baldness




stem cells

First trial to use umbilical cord stem cells to cure HIV




stem cells

Stem cell transplant recipients demystify the fate of donated stem cells




stem cells

Study finds long-term dynamics of transplanted stem cells




stem cells

Stem cells from schizophrenics produce fewer neurons

New research shows that a genetic mutation associated with schizophrenia alters the process of cellular differentiation, disturbing the balance of neurons and glia in the brain

Stem cells obtained from patients with schizophrenia carry a genetic mutation that alters the ratio of the different type of nerve cells they produce, according to a new study by researchers in Japan. The findings, published today in the journal Translational Psychiatry, suggest that abnormal neural differentiation may contribute to the disease, such that fewer neurons and more non-neuronal cells are generated during the earliest stages of brain development.

Schizophrenia is a debilitating mental illness that affects about 1 in 100 people. It is known to be highly heritable, but is genetically complex: so far, researchers have identified over 100 rare genetic variations and dozens of mutations associated with increased risk of developing the disease.

Related: Brain’s immune cells hyperactive in schizophrenia

Related: Turning urine into brain cells | Mo Costandi

Continue reading...




stem cells

Stem cells shown to delay their own death to aid healing




stem cells

​NTU Singapore scientists find easier way to harvest healing factors from adult stem cells in the lab

...




stem cells

Scientists grow bacon from stem cells

Bacon shortages could be a think of fiction. A new technique that turns pig stem cells into strips of meat could offer a green alternative to the slaughterhouse



  • Research & Innovations

stem cells

For stem cells in 30 minutes, just add acid

Japanese researchers have developed a method to quickly create stem cells from almost any other type of cell.



  • Research & Innovations

stem cells

Method and system for preparing soft tissue for grafting, enhancing grafting results, and grafting autologous fat and adipocyte derived stem cells to soft tissue such as the breast and other tissue defects

A method is disclosed for preparing a soft tissue site, and augmenting the soft tissue site, such as the breast(s), scar, depression, or other defect, of a subject through use of devices that exert a distractive force on the breast(s) and grafting of autologous fat tissue such as domes with sealing rims for surrounding each of the soft tissue site and a regulated pump. The method for preparing the soft tissue site, and enhancing fat graft results, entails application of the distracting force to the targeted soft tissue site at least intermittently for some period of time and preferably several weeks prior to the graft procedure. A related aspect of the invention includes following the preparation steps by transfer of fat from other areas of the subject to the subject's soft tissue site, and then reapplication of the distractive force to the soft tissue site that received the autologous fat graft. Alternatively, fat from genetically related sources may be used, and the fat may be further processed prior to injection. Substantial soft tissue augmentation, high rates of graft survival and negligible graft necrosis (data demonstrating 80% survival and only 20% necrosis is presented) or calcification result from the practice of these methods.




stem cells

Methods of expanding embryonic stem cells in a suspension culture

A method of expanding and maintaining human embryonic stem cells (ESCs) in an undifferentiated state by culturing the ESCs in a suspension culture under culturing conditions devoid of substrate adherence is provided. Also provided are a method of deriving ESC lines in the suspension culture and methods of generating lineage-specific cells from ESCs which were expanded in the suspension culture of the present invention.




stem cells

Method of selecting stem cells having high chondrogenic differentiation capability

Thrombospondin 1 (TSP-1), TSP-2, interleukin 17B receptor (IL-17BR) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) associated with stem cell activity and use thereof.




stem cells

Major Improvement in Wound Healing Through Pharmacologic Mobilization of Stem Cells in Severely Diabetic Rats

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow–derived CD133+ and CD34+ endothelial progenitor cells and Ym1/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.




stem cells

More selective elimination of leukemic and hematopoietic stem cells

Acute myeloid leukemia is an aggressive cancer of the blood-forming system. It affects the hematopoietic stem cells, or blood stem cells, of various white blood cells and of the red blood cells and platelets.




stem cells

Bone Stem Cells Located

Title: Bone Stem Cells Located
Category: Health News
Created: 4/27/2010 12:10:00 PM
Last Editorial Review: 4/28/2010 12:00:00 AM




stem cells

Researchers Rejuvenate Blood-Forming Stem Cells in Mice

Title: Researchers Rejuvenate Blood-Forming Stem Cells in Mice
Category: Health News
Created: 5/3/2012 2:05:00 PM
Last Editorial Review: 5/4/2012 12:00:00 AM




stem cells

Stem Cells Used to Regenerate Heart Muscle in Monkeys

Title: Stem Cells Used to Regenerate Heart Muscle in Monkeys
Category: Health News
Created: 4/30/2014 2:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM




stem cells

Transplanted Skin Stem Cells Help Blind Mice See Light

Title: Transplanted Skin Stem Cells Help Blind Mice See Light
Category: Health News
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 12:00:00 AM




stem cells

Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis

Background

Mutations in CTNS—a gene encoding the cystine transporter cystinosin—cause the rare, autosomal, recessive, lysosomal-storage disease cystinosis. Research has also implicated cystinosin in modulating the mTORC1 pathway, which serves as a core regulator of cellular metabolism, proliferation, survival, and autophagy. In its severest form, cystinosis is characterized by cystine accumulation, renal proximal tubule dysfunction, and kidney failure. Because treatment with the cystine-depleting drug cysteamine only slows disease progression, there is an urgent need for better treatments.

Methods

To address a lack of good human-based cell culture models for studying cystinosis, we generated the first human induced pluripotent stem cell (iPSC) and kidney organoid models of the disorder. We used a variety of techniques to examine hallmarks of cystinosis—including cystine accumulation, lysosome size, the autophagy pathway, and apoptosis—and performed RNA sequencing on isogenic lines to identify differentially expressed genes in the cystinosis models compared with controls.

Results

Compared with controls, these cystinosis models exhibit elevated cystine levels, increased apoptosis, and defective basal autophagy. Cysteamine treatment ameliorates this phenotype, except for abnormalities in apoptosis and basal autophagy. We found that treatment with everolimus, an inhibitor of the mTOR pathway, reduces the number of large lysosomes, decreases apoptosis, and activates autophagy, but it does not rescue the defect in cystine loading. However, dual treatment of cystinotic iPSCs or kidney organoids with cysteamine and everolimus corrects all of the observed phenotypic abnormalities.

Conclusions

These observations suggest that combination therapy with a cystine-depleting drug such as cysteamine and an mTOR pathway inhibitor such as everolimus has potential to improve treatment of cystinosis.




stem cells

PIWI-piRNA pathway-mediated transposable element repression in Hydra somatic stem cells [REPORT]

Transposable elements (TEs) can damage genomes, thus organisms use a variety of mechanisms to repress TE expression. The PIWI–piRNA pathway is a small RNA pathway that represses TE expression in the germline of animals. Here we explore the function of the pathway in the somatic stem cells of Hydra, a long-lived freshwater cnidarian. Hydra have three stem cell populations, all of which express PIWI proteins; endodermal and ectodermal epithelial stem cells (ESCs) are somatic, whereas the interstitial stem cells have germline competence. To study somatic function of the pathway, we isolated piRNAs from Hydra that lack the interstitial lineage and found that these somatic piRNAs map predominantly to TE transcripts and display the conserved sequence signatures typical of germline piRNAs. Three lines of evidence suggest that the PIWI–piRNA pathway represses TEs in Hydra ESCs. First, epithelial knockdown of the Hydra piwi gene hywi resulted in up-regulation of TE expression. Second, degradome sequencing revealed evidence of PIWI-mediated cleavage of TE RNAs in epithelial cells using the ping-pong mechanism. Finally, we demonstrated a direct association between Hywi protein and TE transcripts in epithelial cells using RNA immunoprecipitation. Altogether, our data reveal that the PIWI–piRNA pathway represses TE expression in the somatic cell lineages of Hydra, which we propose contributes to the extreme longevity of the organism. Furthermore, our results, in combination with others, suggest that somatic TE repression is an ancestral function of the PIWI–piRNA pathway.




stem cells

Recruiting TP53 to target chronic myeloid leukemia stem cells




stem cells

Suppressive effects of anagrelide on cell cycle progression and the maturation of megakaryocyte progenitor cell lines in human induced pluripotent stem cells




stem cells

Non-Stem Cells Seed Colorectal Cancer Metastases and Gain Stem Traits [Metastasis]

LGR5 cells seed colorectal cancer metastases and produce stemlike LGR5+ outgrowth-promoting cells.




stem cells

[CORRIGENDUM] Corrigendum: Niche Cells and Signals that Regulate Lung Alveolar Stem Cells In Vivo




stem cells

More selective elimination of leukemia stem cells and blood stem cells

Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia. However, the side effects of therapies are often severe. Researchers have now shown how human healthy and cancerous hematopoietic stem cells can be more selectively eliminated using immunotherapy instead of chemotherapy in mice. The aim is to test the new immunotherapy in humans as soon as possible.




stem cells

Stem cells shown to delay their own death to aid healing

A new study shows how stem cells -- which can contribute to creating many parts of the body, not just one organ or body part -- are able to postpone their own death in order to respond to an injury that needs their attention. The study was done in planarians, which are tiny worms used as model organisms to study regeneration because of their ability to recover from any injury using stem cells.




stem cells

More selective elimination of leukemia stem cells and blood stem cells

Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia. However, the side effects of therapies are often severe. A group of researchers led by the University of Zurich have now shown how human healthy and cancerous hematopoietic stem cells can be more selectively eliminated using immunotherapy instead of chemotherapy in mice. The aim is to test the new immunotherapy in humans as soon as possible.




stem cells

Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy




stem cells

Oral health in allogeneic hematopoietic stem cells transplantation survivors




stem cells

Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis




stem cells

ZBP1 (DAI/DLM-1) promotes osteogenic differentiation while inhibiting adipogenic differentiation in mesenchymal stem cells through a positive feedback loop of Wnt/β-catenin signaling




stem cells

Ionomycin ameliorates hypophosphatasia via rescuing alkaline phosphatase deficiency-mediated L-type Ca<sup>2+</sup> channel internalization in mesenchymal stem cells




stem cells

Stem Cells Extracted from Baby Teeth Can Help Regrow Dental Tissues

Dental stem cells extracted from baby teeth can help in the regeneration of dental tissues, reports a new study. The findings of the study are published




stem cells

Delivery of Healthy Donor Stem Cells can Help Correct Bone Disorder

Healthy donor stem cells that produce normal collagen in Osteogenesis imperfecta (OI) patients have the potential to improve bone mass and correct the mutant collagen matrix, reports a new study.




stem cells

Stem Cells Transformed into Bone Using Artificial Muscle Sheets

Researchers discovered a polymer sheet that functions as an artificial muscle as it transforms stem cells into bones. Stem cells are known for their




stem cells

Human Stem Cells Provide Pain Relief in a Single Treatment

Human stem cells can provide long lasting pain relief without producing any side effects, in a single treatment, according to a study done on mice. The