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https://www.readbyqxmd.com/read/29663194/centrosome-inheritance-does-not-regulate-cell-fate-in-granule-neuron-progenitors-of-the-developing-cerebellum
#1
Anindo Chatterjee, Kaviya Chinnappa, Narendrakumar Ramanan, Shyamala Mani
An inherent asymmetry exists between the two centrosomes of a dividing cell. One centrosome is structurally more mature (mother centrosome) than the other (daughter centrosome). Post division, one daughter cell inherits the mother centrosome while the other daughter cell inherits the daughter centrosome. Remarkably, the kind of centrosome inherited is associated with cell fate in several developmental contexts such as in radial glial progenitors in the developing mouse cortex, Drosophila neuroblast divisions and in Drosophila male germline stem cells...
April 16, 2018: Cerebellum
https://www.readbyqxmd.com/read/29659651/stat3-is-required-for-proliferation-and-exhibits-a-cell-type-specific-binding-preference-in-mouse-female-germline-stem-cells
#2
Yunzhao Gu, Jun Wu, Wenxiao Yang, Chao Xia, Xinglong Shi, Hua Li, Jielin Sun, Zhifeng Shao, Ji Wu, Xiaodong Zhao
LIF-mediated STAT3 signaling is critically involved in stem cells and development. However, its function in mouse female germline cells (FGSCs) remains elusive. In this study, we demonstrated that LIF-induced STAT3 activation contributes to the proliferation and undifferentiation maintenance of mouse FGSCs. Characterization of the STAT3-mediated transcriptional network by intersecting ChIP-seq and RNA-seq datasets revealed 405 direct target genes of STAT3, which are primarily involved in proliferation and germline development...
April 16, 2018: Molecular omics
https://www.readbyqxmd.com/read/29649254/uxt-is-required-for-spermatogenesis-in-mice
#3
Eric D Schafler, Phillip A Thomas, Susan Ha, Yu Wang, Keria Bermudez-Hernandez, Zuojian Tang, David Fenyö, Margarita Vigodner, Susan K Logan
Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult...
2018: PloS One
https://www.readbyqxmd.com/read/29628393/in-vivo-genetic-manipulation-of-spermatogonial-stem-cells-and-their-microenvironment-by-adeno-associated-viruses
#4
Satoshi Watanabe, Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Takashi Shinohara
Adeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem cells (SSCs) and their microenvironment via AAV1/9. AAV1/9 microinjected into the seminiferous tubules penetrated both the basement membrane and BTB, thereby transducing not only Sertoli cells and SSCs but also peritubular cells and Leydig cells...
April 2, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29617903/spermatogonial-stem-cells
#5
Hiroshi Kubota, Ralph L Brinster
Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis and have an essential role to maintain highly productive spermatogenesis by self-renewal and continuous generation of daughter spermatogonia that differentiate into spermatozoa, transmitting genetic information to the next generation. Since the 1950s, many experimental methods, including histology, immunostaining, whole-mount analyses, and pulse-chase labeling had been used in attempts to identify SSCs, but without success. In 1994, a spermatogonial transplantation method was reported that established a quantitative functional assay to identify SSCs by evaluating their ability to both self-renew and differentiate to spermatozoa...
March 30, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29615466/lmx1a-is-required-for-the-development-of-the-ovarian-stem-cell-niche-in-drosophila
#6
Andrew W Allbee, Diego E Rincon-Limas, Benoît Biteau
The Drosophila ovary serves as a model for pioneering studies of stem cell niches, with defined cell types and signaling pathways supporting both germline and somatic stem cells. The establishment of the niche units begins during larval stages with the formation of terminal filament-cap structures; however, the genetics underlying their development remains largely unknown. Here we show that the transcription factor Lmx1a is required for ovary morphogenesis. We found that Lmx1a is expressed in early ovarian somatic lineages and becomes progressively restricted to terminal filaments and cap cells...
April 3, 2018: Development
https://www.readbyqxmd.com/read/29594232/increasing-genomic-instability-during-cancer-therapy-in-a-patient-with-li-fraumeni-syndrome
#7
Nadine Schuler, Jan Palm, Sabine Schmitz, Yvonne Lorat, Claudia E Rübe
Background: Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder characterized by germline mutations of the p53 tumor-suppressor gene. In response to DNA damage, p53 stimulates protective cellular processes including cell-cycle arrest and apoptosis to prevent aberrant cell proliferation. Current cancer therapies involve agents that damage DNA, which also affect non-cancerous hematopoietic stem/progenitor cells. Here, we report on a child with LFS who developed genomic instability during craniospinal irradiation for metastatic choroid plexus carcinoma (CPC)...
December 2017: Clinical and Translational Radiation Oncology
https://www.readbyqxmd.com/read/29587218/culture-and-transplantation-of-spermatogonial-stem-cells
#8
Seiji Takashima, Takashi Shinohara
The spermatogonial transplantation technique was developed by Dr. Ralph Brinster in 1994. Transplanted spermatogonial stem cells (SSCs) produce germ cell colonies after microinjection into the seminiferous tubules of infertile mice. This technique provided the first functional assay for SSCs. Although it became possible to produce transgenic animals using this transplantation technique in 2001, the lack of SSC culture systems prevented efficient genetic manipulation. To overcome this problem, a long-term SSC culture technique was developed in 2003...
March 15, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29584704/roles-of-mitochondrial-dna-mutations-in-stem-cell-ageing
#9
REVIEW
Tianhong Su, Doug M Turnbull, Laura C Greaves
Mitochondrial DNA (mtDNA) mutations accumulate in somatic stem cells during ageing and cause mitochondrial dysfunction. In this review, we summarize the studies that link mtDNA mutations to stem cell ageing. We discuss the age-related behaviours of the somatic mtDNA mutations in stem cell populations and how they potentially contribute to stem cell ageing by altering mitochondrial properties in humans and in mtDNA-mutator mice. We also draw attention to the diverse fates of the mtDNA mutations with different origins during ageing, with potential selective pressures on the germline inherited but not the somatic mtDNA mutations...
March 27, 2018: Genes
https://www.readbyqxmd.com/read/29578412/cytokine-receptor-eb1-interaction-couples-cell-polarity-and-fate-during-asymmetric-cell-division
#10
Cuie Chen, Ryan Cummings, Aghapi Mordovanakis, Alan J Hunt, Michael Mayer, David Sept, Yukiko M Yamashita
Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs)...
March 26, 2018: ELife
https://www.readbyqxmd.com/read/29575491/optimization-of-reprogramming-culture-condition-for-the-generation-of-induced-pluripotent-stem-cells-from-col1a1-4f2a-oct4-gfp-mice-with-high-efficiency
#11
Po-Ying Lin, Sheng-Chieh Hsu, Hung-Chi Chen, Wen-Bin Len, Fang-Chi Hsiao, Mei-Chun Liu, Pei-Ling Pan, Tsai-Chen Lin, Ying-Hsuan Lee, Yaa-Jyuhn James Meir
A reprogrammable transgenic mouse strain, called Col1a1 4F2A-Oct4-GFP, was bred for the present study. Because the somatic cells of this mouse strain contain only two copies of each Yamanaka factor, these animals are inefficient at producing iPSCs (approx. 0.005%) under traditional culture conditions. With an optimized culture condition, the iPSC production rate of MEFC ol1a1 4F2A-Oct4- GFP was increased approximately to 8%. Further, promotion of cell proliferation by serum supplementation did not enhance iPSC production...
March 25, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29559475/germline-mutations-in-lysine-specific-demethylase-1-lsd1-kdm1a-confer-susceptibility-to-multiple-myeloma
#12
Xiaomu Wei, M Nieves Calvo-Vidal, Siwei Chen, Gang Wu, Maria V Revuelta, Jian Sun, Jinghui Zhang, Michael F Walsh, Kim E Nichols, Vijai Joseph, Carrie Snyder, Celine M Vachon, James D McKay, Shu-Ping Wang, David S Jayabalan, Lauren M Jacobs, Dina Becirovic, Rosalie G Waller, Mykyta Artomov, Agnes Viale, Jayeshkumar Patel, Jude M Phillip, Selina Chen-Kiang, Karen Curtin, Mohamed Salama, Djordje Atanackovic, Ruben Niesvizky, Ola Landgren, Susan L Slager, Lucy A Godley, Jane Churpek, Judy E Garber, Kenneth C Anderson, Mark J Daly, Robert G Roeder, Charles Dumontet, Henry T Lynch, Charles G Mullighan, Nicola J Camp, Kenneth Offit, Robert J Klein, Haiyuan Yu, Leandro Cerchietti, Steven M Lipkin
Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29555651/an-inactivating-mutation-in-the-histone-deacetylase-sirt6-causes-human-perinatal-lethality
#13
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29549109/diet-regulates-membrane-extension-and-survival-of-niche-escort-cells-for-germline-homeostasis-via-insulin-signaling
#14
Yu-Han Su, Elham Rastegri, Shih-Han Kao, Chun-Min Lai, Kun-Yang Lin, Hung-Yu Liao, Mu-Hsiang Wang, Hwei-Jan Hsu
Diet is an important regulator of stem cell homeostasis, however, the underlying mechanisms of this regulation are not fully known. Here, we report that insulin signaling mediates dietary maintenance of Drosophila ovarian germline stem cells (GSCs) by promoting the extension of niche escort cell (EC) membranes to wrap around GSCs. This wrapping may facilitate the delivery of BMP stemness factors from ECs in the niche to GSCs. In addition to the effects on GSCs, insulin signaling-mediated regulation of EC number and protrusions controls the division and growth of GSC progeny...
March 16, 2018: Development
https://www.readbyqxmd.com/read/29531804/modeling-cancer-using-patient-derived-induced-pluripotent-stem-cells-to-understand-development-of-childhood-malignancies
#15
REVIEW
Ana Marin Navarro, Evelyn Susanto, Anna Falk, Margareta Wilhelm
In vitro modeling of complex diseases is now a possibility with the use of patient-derived induced pluripotent stem (iPS) cells. Their stem cell properties, including self-renewal and their potential to virtually differentiate into any cell type, emphasize their importance as a translational tool for modeling disorders that so far have been limited by the unavailability of primary cell lines, animal models, or inaccessible human materials. Around 100 genes with germline mutations have been described to be responsible for cancer predisposition...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29518209/a-germline-specific-role-for-the-mtorc2-component-rictor-in-maintaining-spermatogonial-differentiation-and-intercellular-adhesion-in-mouse-testis
#16
Shun Bai, Le Cheng, Yingwen Zhang, Chunsen Zhu, Zhiping Zhu, Ruping Zhu, C Yan Cheng, Lan Ye, Ke Zheng
STUDY QUESTION: What is the physiological role of Rictor in spermatogenic cells? SUMMARY ANSWER: Germline expression of Rictor regulates spermatogonial differentiation and has an essential role in coordinating germ cells and Sertoli cells in maintaining intact cell-cell adhesion dynamics and cytoskeleton-based architecture in the seminiferous epithelium. WHAT IS KNOWN ALREADY: The mechanistic target of rapamycin (mTOR) resides in its functions as the catalytic subunits of the structurally and functionally distinct mTORC1 and mTORC2 complexes...
February 6, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29507057/the-molecular-chaperone-hsp90-promotes-notch-signaling-in-the-germline-of-caenorhabditis-elegans
#17
James L Lissemore, Elyse Connors, Ying Liu, Li Qiao, Bing Yang, Mark L Edgley, Stephane Flibotte, Jon Taylor, Vinci Au, Donald G Moerman, Eleanor M Maine
In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40 , defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90 , previously known as daf-21 , which encodes the C...
March 5, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29501710/suppression-of-dsrna-response-genes-and-innate-immunity-following-oct4-stella-and-nanos2-overexpression-in-mouse-embryonic-fibroblasts
#18
Moein Farshchian, Maryam M Matin, Olivier Armant, Dirk Geerts, Mahtab Dastpak, Saeideh Nakhaei-Rad, Massoumeh Tajeran, Amir Jebelli, Mina Shahriyari, Monireh Bahrami, Ali Fallah, Vesal Yaghoobi, Mahdi Mirahmadi, Mohammad Reza Abbaszadegan, Ahmad Reza Bahrami
The self-renewal capacity of germline derived stem cells (GSCs) makes them an ideal source for research and use in clinics. Despite the presence of active gene network similarities between embryonic stem cells (ESCs) and GSCs, there are unanswered questions regarding the roles of evolutionary conserved genes in GSCs. To determine the reprogramming potential of germ cell- specific genes, we designed a polycistronic gene cassette expressing Stella, Oct4 and Nanos2 in a lentiviral-based vector. Deep transcriptome analysis showed the activation of a set of pluripotency and germ-cell-specific markers and the downregulation of innate immune system...
March 1, 2018: Cytokine
https://www.readbyqxmd.com/read/29495453/wnt-signaling-in-stem-cell-maintenance-and-differentiation-in-the-drosophila-germarium
#19
REVIEW
Indrayani Waghmare, Andrea Page-McCaw
Wnt signaling is a conserved regulator of stem cell behaviors, and the Drosophila germarium has been an important model tissue for the study of stem cell maintenance, differentiation, and proliferation. Here we review Wnt signaling in the germarium, which houses two distinct types of ovarian stem cells: the anteriorly located germline stem cells (GSCs), which give rise to oocytes; and the mid-posteriorly located follicle stem cells (FSCs), which give rise to the somatic follicle cells that cover a developing oocyte...
February 27, 2018: Genes
https://www.readbyqxmd.com/read/29488325/resilience-to-aging-in-the-regeneration-capable-flatworm-macrostomum-lignano
#20
Stijn Mouton, Magda Grudniewska, Lisa Glazenburg, Victor Guryev, Eugene Berezikov
Animals show a large variability of lifespan, ranging from short-lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation-by-regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free-living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed...
February 28, 2018: Aging Cell
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