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Stem Cells

Haoyuan Li, Yanmin Zhang, Shangming Liu, Fengpeng Li, Benlin Wang, Jianjie Wang, Lanfang Cao, Tongliang Xia, Qingyu Yao, Haijun Chen, Yulin Zhang, Xiaodong Zhu, Yang Li, Gang Li, Jian Wang, Xingang Li, Shilei Ni
Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes...
January 14, 2019: Stem Cells
Julie R Beegle
No abstract text is available yet for this article.
January 12, 2019: Stem Cells
Andrew T Crane, Joseph P Voth, Francis X Shen, Walter C Low
Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered pre-implantation animal embryos eventually giving rise to fully developed human tissues and organs within the animal host for use in regenerative medicine. The ethical issues surrounding this method have caused the National Institutes of Health to issue a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal...
January 10, 2019: Stem Cells
Kelli I Korski, Dieter A Kubli, Bingyan J Wang, Farid G Khalafalla, Megan M Monsanto, Fareheh Firouzi, Oscar H Echeagaray, Taeyong Kim, Robert M Adamson, Walter P Dembitsky, Åsa B Gustafsson, Mark A Sussman
Senescence-associated dysfunction deleteriously affects biological activites of human c-Kit+ cardiac progenitor cells (hCPCs), particularly under conditions of in vitro culture. In comparison, preservation of self-renewal and decreases in mitochondrial reactive oxygen species (ROS) are characteristic of murine CPCs in vivo that reside within hypoxic niches. Recapitulating hypoxic niche oxygen tension conditions of ~1% O2 in vitro for expansion of hCPCs rather than typical normoxic cell culture conditions (21% O2 ) could provide significant improvement of functional and biological activity of hCPCs...
January 10, 2019: Stem Cells
Nathaniel H Boyd, Kiera Walker, Adetokunbo Ayokanmbi, Emily R Gordon, Julia Whetsel, Cynthia M Smith, Richard G Sanchez, Farah Lubin, Asmi Chakraborty, Anh Nhat Tran, Cameron Herting, Dolores Hambardzumyan, G Yancey Gillespie, James R Hackney, Sara J Cooper, Kai Jiao, Anita B Hjelmeland
Tumorigenic and non-neoplastic tissue injury occurs via the ischemic microenvironment defined by low oxygen, pH, and nutrients due to blood supply malfunction. Ischemic conditions exist within regions of pseudopalisading necrosis, a pathological hallmark of glioblastoma (GBM), the most common primary malignant brain tumor in adults. To recapitulate the physiologic microenvironment found in GBM tumors and tissue injury, we developed an in vitro ischemic model and identified chromodomain helicase DNA binding protein 7 (CHD7) as a novel ischemia-regulated gene...
January 10, 2019: Stem Cells
Zhenbo Han, Ying Yu, Juan Xu, Zhengyi Bao, Zihang Xu, Jiancheng Hu, Meixi Yu, Djibril Bamba, Wenya Ma, Fengzhi Ding, Lai Zhang, Mengyu Jin, Gege Yan, Qi Huang, Xiuxiu Wang, Bingjie Hua, Fan Yang, Yuan Li, Lei Lei, Nan Cao, Zhenwei Pan, Benzhi Cai
Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self-renewal of hPSCs as well as spontaneous and nonspecific differentiation. Moreover, long-term depletion of iron can result in the remarkable cell death of hPSCs via apoptosis and necrosis pathways...
December 31, 2018: Stem Cells
M Vlaski-Lafarge, D Loncaric, L Perez, V Labat, C Debeissat, P Brunet de la Grange, R Rossignol, Z Ivanovic, H Bœuf
mESCs are endowed by a time-dependent window of plasticity during their early commitment steps. Indeed, while mESCs deprived of LIF for 24 h revert to their naive pluripotent state after subsequent LIF re-addition, cells deprived of LIF for 48 h are no longer efficient in reverting, upon LIF addition, and undergo irreversible differentiation. We investigated undisclosed bioenergetic profiles of early mESC-derived committed cells versus their undifferentiated states in order to reveal specific bioenergetic changes associated with mESC plasticity...
December 31, 2018: Stem Cells
Federica Todaro, Federica Campolo, Florencia Barrios, Manuela Pellegrini, Silvia Di Cesare, Lino Tessarollo, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Kit is a growth factor receptor that regulates proliferation and/or survival of many embryonic and postnatal stem cell types. When mutated, it can induce malignant transformation of the host cells. To dissect the Kit role in the control of ESC pluripotency, we studied its expression during early mouse embryogenesis and during the process of ESC derivation from inner cell mass (ICM) cells. We followed the in vitro development of early mouse embryos obtained from transgenic mice carrying Kit promoter regions fused to EGFP (Kit-EGFP) and found that they initiate EGFP expression at morula stage...
December 19, 2018: Stem Cells
Bin Jiang, Yan Li, Xiaoyan Wang, Enqin Li, Kyle Murphy, Kyle Vaccaro, Yingcui Li, Ren-He Xu
Despite of the long discrepancy over their definition, heterogeneity, and functions, mesenchymal stromal/stem cells (MSCs) have proved to be a key player in tissue repair and homeostasis. Generally, somatic tissue-derived MSCs (st-MSCs) are subject to quality variations related to donated samples and biosafety concern for transmission of potential pathogens from the donors. In contrast, human pluripotent stem cells (hPSCs) are unlimited in supply, clear in the biological background, and convenient for quality control, genetic modification and scale-up production...
December 18, 2018: Stem Cells
Joseph Collin, Rachel Queen, Darin Zerti, Birthe Dorgau, Rafiqul Hussain, Jonathan Coxhead, Simon Cockell, Majlinda Lako
The rapid improvements in single cell sequencing technologies and analyses afford greater scope for dissecting organoid cultures composed of multiple cell types and create an opportunity to interrogate these models to understand tissue biology, cellular behaviour and interactions. To this end, retinal organoids generated from human embryonic stem cells (hESCs) were analysed by single cell RNA-sequencing (scRNA-Seq) at three time points of differentiation. Combinatorial data from all time points revealed the presence of nine clusters, five of which corresponded to key retinal cell types: retinal pigment epithelium (RPE), retinal ganglion cells (RGCs), cone and rod photoreceptors and Müller glia...
December 12, 2018: Stem Cells
Li-Jie Zhang, Cen Yan, Sarah Schouteden, Xiao-Juan Ma, Dong Zhao, Thorsten Peters, Catherine M Verfaillie, Ying-Mei Feng
RATIONALE: Previously we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between β2-/- and β2+/+ mice, transplantation of β2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than β2+/+ BMC. OBJECTIVE: To address if integrin β2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. METHODS AND RESULTS: FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor (MEP) frequency and cell number were lower in β2-/- mice than β2+/+ mice...
December 11, 2018: Stem Cells
Jan A Nolta
No abstract text is available yet for this article.
December 11, 2018: Stem Cells
Julie R Beegle
No abstract text is available yet for this article.
December 11, 2018: Stem Cells
Swarnabh Bhattacharya, Laura Serror, Eshkar Nir, Dalbir Dhiraj, Anna Altshuler, Maroun Khreish, Beatrice Tiosano, Peleg Hasson, Lia Panman, Chen Luxenburg, Daniel Aberdam, Ruby Shalom-Feuerstein
Mutations in key transcription factors SOX2 and P63 were linked with developmental defects and post-natal abnormalities such as corneal opacification, neovascularization and blindness. The latter phenotypes suggest that SOX2 and P63 may be involved in corneal epithelial regeneration. While P63 has been shown to be a key regulator of limbal stem cells (LSCs), the expression pattern and function of SOX2 in the adult cornea remained unclear. Here we show that SOX2 regulates P63 to control corneal epithelial stem/progenitor cell function...
December 10, 2018: Stem Cells
Chieh Tseng, Krishna Sinha, Haiying Pan, Yan Cui, Ping Guo, Chih Yi Lin, Fan Yang, Zhenhan Deng, Holger K Eltzschig, Aiping Lu, Johnny Huard
The "super-healing" Murphy Roths Large (MRL/MpJ) mouse possesses a superior regenerative capacity for repair of many tissues, which makes it an excellent animal model for studying molecular and cellular mechanisms during tissue regeneration. Since the role of muscle progenitor cells (MPCs) in muscle healing capacity of MRL/MpJ mice has not been previously studied, we investigated the muscle regenerative capacity of MRL/MpJ mice following muscle injury, and the results were compared to results from C57BL/6 J (B6) age-matched control mice...
December 10, 2018: Stem Cells
Ahmad Abu-Khader, Kyle W Law, Suria Jahan, Javed K Manesia, Roya Pasha, Owen Hovey, Nicolas Pineault
Ex vivo expansion of hematopoietic stem cell (HSCs) and progenitors may one day overcome the slow platelet engraftment kinetics associated with umbilical cord blood transplantation. Serum-free medium conditioned with osteoblasts (i.e., osteoblast-conditioned medium [OCM]) derived from mesenchymal stromal cells (MSC) was previously shown to increase cell growth and raise the levels of human platelets in mice transplanted with OCM-expanded progenitors. Herein, we characterized the cellular and molecular mechanisms responsible for these osteoblast-derived properties...
December 5, 2018: Stem Cells
Irina Neganova, Lewis Cotts, Peter Banks, Katja Gassner, Lyle Armstrong, Graham Ladds, Majlinda Lako
Direct reprogramming of human somatic cells toward induced pluripotent stem cells holds great promise for regenerative medicine and basic biology. We used a high-throughput siRNA screening assay in the initiation phase of reprogramming for 784 genes belonging to kinase and phosphatase families and identified 68 repressors and 22 effectors. Six new candidates belonging to the family of the G protein-coupled receptors (GPCRs) were identified suggesting an important role for this key signalling pathway during somatic cell induced reprogramming...
December 4, 2018: Stem Cells
Abbas Jafari, Adiba Isa, Li Chen, Nicholas Ditzel, Walid Zaher, Linda Harkness, Hans E Johnsen, Basem M Abdallah, Christian Clausen, Moustapha Kassem
Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level...
November 28, 2018: Stem Cells
Pooja Chaudhari, Lipeng Tian, Amy Kim, Qingfeng Zhu, Robert Anders, Kathleen B Schwarz, Saul Sharkis, Zhaohui Ye, Yoon-Young Jang
Directed differentiation of human induced pluripotent stem cells (iPSCs) toward hepatobiliary lineages has been increasingly used as models of human liver development/diseases. As protein kinases are important components of signaling pathways regulating cell fate changes, we sought to define the key molecular mediators regulating human liver development using inhibitors targeting tyrosine kinases during hepatic differentiation of human iPSCs. A library of tyrosine kinase inhibitors was used for initial screening during the multi-stage differentiation of human iPSCs to hepatic lineage...
November 24, 2018: Stem Cells
Jin Seok Park, Minbeom Kim, No-Joon Song, Jun-Hyeong Kim, Dongyeob Seo, Ji-Hyung Lee, Su Myung Jung, Jae Young Lee, Jaewon Lee, Youn Sook Lee, Kye Won Park, Seok Hee Park
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into mature cells of various cell types. Although the differentiation process of MSCs requires lineage-specific transcription factors, the exact molecular mechanism that determine MSCs differentiation is not clearly addressed. Here, we demonstrate a Smad4-Taz axis as a new intrinsic regulator for adipo-osteogenic differentiation of MSCs and show that this function of Smad4 is independent of the TGF-β signal. Smad4 directly bound to the Taz protein and facilitated nuclear localization of Taz through its nuclear localization signal (NLS)...
November 16, 2018: Stem Cells
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