scholarly journals Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell–enriched Population by Stimulating Their Differentiation

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Shimeng Liu ◽  
Ping Yin ◽  
Jingting Xu ◽  
Ariel J Dotts ◽  
Stacy A Kujawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Cell Population ◽  
Uterine Leiomyoma ◽  
Stem Cell Population ◽  
Epigenetic Landscape ◽  
Stem Cell Regulation ◽  
Integrative Analyses ◽  
Associated Functions ◽  
Intermediate Cells

Abstract Uterine leiomyoma (LM) is the most common tumor in women and can cause severe morbidity. Leiomyoma growth requires the maintenance and proliferation of a stem cell population. Dysregulated deoxyribonucleic acid (DNA) methylation has been reported in LM, but its role in LM stem cell regulation remains unclear. Here, we fluorescence-activated cell sorting (FACS)-sorted cells from human LM tissues into 3 populations: LM stem cell–like cells (LSC, 5%), LM intermediate cells (LIC, 7%), and differentiated LM cells (LDC, 88%), and we analyzed the transcriptome and epigenetic landscape of LM cells at different differentiation stages. Leiomyoma stem cell–like cells harbored a unique methylome, with 8862 differentially methylated regions compared to LIC and 9444 compared to LDC, most of which were hypermethylated. Consistent with global hypermethylation, transcript levels of TET1 and TET3 methylcytosine dioxygenases were lower in LSC. Integrative analyses revealed an inverse relationship between methylation and gene expression changes during LSC differentiation. In LSC, hypermethylation suppressed the genes important for myometrium- and LM-associated functions, including muscle contraction and hormone action, to maintain stemness. The hypomethylating drug, 5′-Aza, stimulated LSC differentiation, depleting the stem cell population and inhibiting tumor initiation. Our data suggest that DNA methylation maintains the pool of LSC, which is critical for the regeneration of LM tumors.

The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis

2017 ◽  
Vol 53 ◽  
pp. S105
Author(s):  
Alexander Gerbaulet ◽  
Kristina Schoedel ◽  
Mina Morcos ◽  
Thomas Zerjatke ◽  
Ingo Roeder ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Hematopoietic Stem

scholarly journals Lrig1 Expression Defines a Distinct Multipotent Stem Cell Population in Mammalian Epidermis

2009 ◽  
Vol 4 (5) ◽  
pp. 427-439 ◽  
Author(s):  
Kim B. Jensen ◽  
Charlotte A. Collins ◽  
Elisabete Nascimento ◽  
David W. Tan ◽  
Michaela Frye ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Multipotent Stem Cell

scholarly journals The presumptive gastric corpus stem cell population is CD44‐positive and expands during metaplasia via increased ERK‐MAPK signaling

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Shradha Khurana ◽  
Won Jae Huh ◽  
Benjamin Moore ◽  
Terrence Riehl ◽  
William F Stenson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Population ◽  
Mapk Signaling ◽  
Stem Cell Population ◽  
Erk Mapk ◽  
Gastric Corpus

scholarly journals 3D Differentiation Of Mammosphere Derived Macaca fascicularis’s Mammary Stem Cells

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Silmi Mariya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Population ◽  
Mammary Stem Cell ◽  
Stem Cell Population ◽  
Stem Cell Markers ◽  
Mammary Stem Cells ◽  
Surgical Biopsy ◽  
Mammary Stem

The mammary gland contains adult stem cells that are capable of self-renewal.  This population plays an important role in the development of mammary gland and breast cancer pathogenesis. The studies of mammary stem cells are limited due to the difficulty to acquire and expand adult stem cell population in an undifferentiated state. In this study, we developed mammosphere cultures of nulliparous cynomolgus monkeys (Macaca fascicularis; Mf) as a culture system to enrich mammary stem cells. This species has similarity of mammary gland structure as humans including anatomy, developmental stages, and lobule profile of mammary gland. The use of stem cells from primate animals is essential to bridge the knowledge gaps resulting from stem cell research using rodents for clinical trials in human. Small samples of mammary tissues were collected by surgical biopsy; cells were cultured as monolayer and cryopreserved. Cryopreserved cells were cultured into mammospheres, and the expression of markers for mammary stem cells was evaluated using qPCR. Cells were further differentiated with 3D approaches to evaluate morphology and organoid budding. The study showed that mammosphere culture resulted in an increase in the expression of mammary stem cell markers with each passage. The 3D differentiation in matrigel allowed for organoid formation. Mammary gland stem cells have been successfully differentiated which characterized by CSN2 marker expression and differentiation regulators marker STAT5 and GATA3. The results indicate that mammospheres can be successfully developed derived from breast tissue of nulliparous Mf collected via surgical biopsy. As the mammosphere allows for enrichment of mammary stem cell population, the findings also suggest that a 3-dimensional system is efficient as in-vitro model to study mammary stem cells and a useful system to study mammary differentiation in regards to cancer prevention.

scholarly journals PIWIL1 Drives Chemoresistance in Multiple Myeloma by Modulating Mitophagy and the Myeloma Stem Cell Population

2022 ◽  
Vol 11 ◽  
Author(s):  
Yajun Wang ◽  
Lan Yao ◽  
Yao Teng ◽  
Hua Yin ◽  
Qiuling Wu
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Stem Cell ◽  
Cell Population ◽  
Side Population ◽  
Chemotherapeutic Agents ◽  
Stem Cell Population ◽  
Exact Function

As an important member of the Argonaute protein family, PIWI-like protein 1 (PIWIL1) plays a key role in tumor cell viability. However, the exact function of PIWIL1 in multiple myeloma (MM) and the underlying mechanism remain unclear. Here, we revealed that PIWIL1 was highly expressed in myeloma cell lines and newly diagnosed MM patients, and that its expression was notably higher in refractory/relapsed MM patients. PIWIL1 promoted the proliferation of MM cells and conferred resistance to chemotherapeutic agents both in vitro and in vivo. More importantly, PIWIL1 enhanced the formation of autophagosomes, especially mitophagosomes, by disrupting mitochondrial calcium signaling and modulating mitophagy-related canonical PINK1/Parkin pathway protein components. Mitophagy/autophagy inhibitors overcome PIWIL1-induced chemoresistance. In addition, PIWIL1 overexpression increased the proportion of side population (SP) cells and upregulated the expression of the stem cell-associated genes Nanog, OCT4, and SOX2, while its inhibition resulted in opposite effects. Taken together, our findings demonstrated that PIWIL1 induced drug resistance by activating mitophagy and regulating the MM stem cell population. PIWIL1 depletion significantly overcame drug resistance and could be used as a novel therapeutic target for reversing resistance in MM patients.

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