STEM CELLS

Cover image for Vol. 34 Issue 6

Stem Cells Express (Accepted Articles - Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Edited By: Jan A. Nolta

Impact Factor: 5.902

ISI Journal Citation Reports © Ranking: 2015: 3/21 (CELL & TISSUE ENGINEERING); 8/70 (Hematology); 14/161 (Biotechnology & Applied Microbiology); 24/213 (Oncology); 34/187 (Cell Biology)

Online ISSN: 1549-4918

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  1. 1 - 35
  1. Tissue-Specific Stem Cells

    1. Mesenchymal Stromal Cells are Readily Recoverable from Lung Tissue, but not the Alveolar Space, in Healthy Humans

      KA Sinclair, ST Yerkovich, T Chen, JL McQualter, PA Hopkins, CA Wells and DC Chambers

      Accepted manuscript online: 29 JUN 2016 04:05AM EST | DOI: 10.1002/stem.2419

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      Human mesenchymal stromal cells were isolated from healthy parenchymal lung tissue (LT-MSCs, n=24, 4 samples from 6 patients) and lung allograft bronchoalveolar lavage fluid (BAL-MSCs, n=12, 1 sample from 12 patients) and gene expression was analysed by microarray. Using Significance Analysis of Microarrays, 105 differentially expressed genes were identified. When visualised as a hierarchical cluster, MSC populations segregate into two distinct groups when samples and probes are clustered using Pearson correlation. Genes that were upregulated in BAL-MSCs include those associated with cellular migration, transforming growth factor-β activation and fibroblastic differentiation. Our findings suggested that BAL-MSCs are a dysregulated population of tissue resident MSCs and may contribute to allograft fibrosis.

  2. Cancer Stem Cells

    1. TGFβ-Responsive HMOX1 Expression is Associated with Stemness and Invasion in GBM

      Dhiman Ghosh, Ilya V. Ulasov, LiPing Chen, Karolina Wallenborg, Parvinder Hothi, Leroy Hood and Charles S. Cobbs

      Accepted manuscript online: 29 JUN 2016 03:50AM EST | DOI: 10.1002/stem.2411

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      Targeted proteomic analyses revealed elevated expressions of transmembrane proteins HMOX1 and SLC16A1 on the surface of glioblastoma cancer stem cells (CSCs) relative to healthy neural stem cells (NSCs). In the hypoxic region of the tumor, these proteins were found to be expressed among pseudopalisading glioma cells that also express known stem cell factors. From biological assays that are known to evaluate stemness, HMOX1 expression was found to be associated with stemness that could be regulated through TGFβ and PTEN signaling networks. Additionally, siRNA mediated inhibition of HMOX1 expression impaired cancer cell invasion. Together, this study demonstrates the association of HMOX1 expression with cancer stemness in glioblastoma and suggests a possible regulatory mechanism of CSC invasion and survival in the hypoxic region of the tumor.

  3. Tissue-Specific Stem Cells

    1. Hyaluronan Upregulates Mitochondrial Biogenesis and Reduces ATP Production for Efficient Mitochondrial Function in Slow-Proliferating Human Mesenchymal Stem Cells

      Mairim Alexandra Solis, Yau-Huei Wei, Chiung-Hsin Chang, Chen-Hsiang Yu, Pao-Lin Kuo and Lynn L.H. Huang

      Accepted manuscript online: 29 JUN 2016 03:50AM EST | DOI: 10.1002/stem.2404

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      Hyaluronan is a key player in the maintenance of slow-proliferative human mesenchymal stem cells through the upregulation of mitochondrial-biogenesis related genes (PGC1-α and mTFA) leading to upregulation of mitochondrial biogenesis (mtDNA, mtMass), mitochondrial function (ATP, OCR, MMP) and mitochondrial respiration with reduced ROS levels and eventual reduced ATP production, as a means of utilizing more efficiently functional mitochondria.

    2. Obesity and Type 2 Diabetes Alters the Immune Properties of Human Adipose Derived Stem Cells

      Carolina Serena, Noelia Keiran, Victoria Ceperuelo-Mallafre, Miriam Ejarque, Rosa Fradera, Kelly Roche, Catalina Nuñez-Roa, Joan Vendrell and Sonia Férnandez-Veledo

      Accepted manuscript online: 29 JUN 2016 02:15AM EST | DOI: 10.1002/stem.2429

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      It is known that obesity increases proliferation of ASCs but reduces their adipogenic differentiation capacity. This study reveals that ASCs from healthy (lean) individuals exhibit typical immunosuppressive activities such as induction of the M2 macrophage phenotype and suppression of T and B cell proliferation. By contrast, ASCs isolated from obese and T2D subjects promote the M1 macrophage phenotype and are less efficient in suppressing lymphocyte proliferation. Thus, obesity and T2D not only disrupt adipose tissue remodeling but also compromise the immunoregulatory properties of ASCs.

  4. Regenerative Medicine

    1. Angiopellosis as an Alternative Mechanism of Cell Extravasation

      Tyler A. Allen, David Gracieux, Maliha Talib, Debra A. Tokarz, M. Taylor Hensley, Jhon Cores, Adam Vandergriff, Junnan Tang, James B.M. de Andrade, Phuong-Uyen Dinh, Jeffrey A. Yoder and Ke Cheng

      Accepted manuscript online: 28 JUN 2016 06:45AM EST | DOI: 10.1002/stem.2451

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      Graphical Abstract

      A stem cell during the middle of the Angiopellosis process. The cell is in the process of extravasating from the inside the lumen of a blood vessel, into the surrounding area. The endothelial cells of the blood vessel are seen remodeling themselves around the cell, as it is removed from the lumen.

  5. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Human Embryonic Stem Cells – What Have We Done? What Are We Doing? Where Are We Going?

      Dusko Ilic and Caroline Ogilvie

      Accepted manuscript online: 28 JUN 2016 03:26AM EST | DOI: 10.1002/stem.2450

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      Ethical issues, the regulatory landscape, and the limited spectrum of diseases were all drawbacks of hESC lines that hiPSC did not have. It is to expect that in foreseeable future hiPSC will take over hESC in both research and clinical applications.

    2. TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming

      Denise Catherine Miles, Nienke Alexandra de Vries, Santiago Gisler, Cor Lieftink, Waseem Akhtar, Ewa Gogola, Inka Pawlitzky, Danielle Hulsman, Ellen Tanger, Martijn Koppens, Roderick Leonardus Beijersbergen and Maarten van Lohuizen

      Accepted manuscript online: 28 JUN 2016 03:26AM EST | DOI: 10.1002/stem.2453

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      Model of TRIM28 function during reprogramming

      A) Ectopic expression of Oct4, Sox2, Klf4 and c-Myc (OSKM) induces the reprogramming of somatic cells into induced pluripotent stem cells at a low efficiency B) Ectopic expression of OSKM along with knock down of TRIM28 increases the expression of genes nearby H3K9me3, and induces the expression of endogenous retroviruses. This decondensed chromatin state increases the reprogramming efficiency.

  6. Tissue-Specific Stem Cells

    1. Transcription Factor GLIS3: a New and Critical Regulator of Postnatal Stages of Mouse Spermatogenesis

      Hong Soon Kang, Liang-Yu Chen, Kristin Lichti-Kaiser, Grace Liao, Kevin Gerrish, Carl D. Bortner, Humphrey H-C. Yao, Edward M. Eddy and Anton M. Jetten

      Accepted manuscript online: 28 JUN 2016 03:26AM EST | DOI: 10.1002/stem.2449

    2. NANOG reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

      Panagiotis Mistriotis, Vivek K. Bajpai, Xiaoyan Wang, Na Rong, Aref Shahini, Mohammadabad Asmani, Mao-shih Liang, Jianmin Wang, Pedro Lei, Song Liu, Ruogang Zhao and Stelios T. Andreadis

      Accepted manuscript online: 28 JUN 2016 03:26AM EST | DOI: 10.1002/stem.2452

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      NANOG restores the myogenic and contractile capacity of senescent stem cells and progeria derived myofibro-blasts. Hair follicle derived Mesenchymal Stem Cells (MSC) were transduced with a tetracycline regulatable vector that carries the NANOG gene. This system allows NANOG expression only when cells are treated with the tetracycline analogue, Doxycycline. Cells were serially passaged until they became senescent (late passage, LP MSC). Subsequently Dox was added to the culture medium (LP NANOG MSC) and the myogenic capacity was evaluated and compared to early passage (EP) MSC cells. Similar experiments were also performed with myofibroblasts derived from patients with an accelerating aging disease (Hutchinson-Gilford Progeria Syndrome, (HGPS). (A-B): Western Blot for ACTA2 and SRF. (C-D) SRF dependent transcriptional activity (CArG-box). (E-F) Immunocytochemistry for ACTA2 (G-H): Contrac-tile force using 3D collagen microtissue. (I): Schematic illustration describing the effects of NANOG on senescent cells. GM: Growth Medium, DM: Differentiation Medium. Scale bar: 20μm for immunocytochemistry and 200μm for the microtissues, Data are presented as mean ± standard deviation, n=3, *: designates statistical significance as compared to LP, LP DM or HGPS, HGPS DM (p<0.05), #: designates statistical significance as compared to LP NANOG GM or HGPS NANOG GM (p<0.05).

  7. Translational and Clinical Research

    1. Human Mesenchymal Stem Cell-Derived Microvesicles Prevent the Rupture of Intracranial Aneurysm in Part by Suppression of Mast Cell Activation via a PGE2-Dependent Mechanism

      Jia Liu, Atsushi Kuwabara, Yoshinobu Kamio, Shuling Hu, Jeonghyun Park, Tomoki Hashimoto and Jae-Woo Lee

      Accepted manuscript online: 28 JUN 2016 03:21AM EST | DOI: 10.1002/stem.2448

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      Effects of intravenous administration of human MSC-derived MVs in the rupture of intracranial aneurysms. (A) Sche-matic diagram of experimental protocol to examine MVs treatment in a mouse model of aneurysm. (B-D) Incidence of aneurysm formation (unruptured and ruptured) (B), aneurysmal rupture rate (C) and symptom-free curve (Kaplan-Meier analysis curve) (D) were examined within 21 days after aneurysm induction in mice treated with vehicle (PBS) or MVs. In (D), the vertical dash lines indicate the time point of MVs or vehicle administration. Mice with aneurysm-free were excluded from graphs in (C) and (D). (E) Representative pictures of normal brain, unruptured and ruptured aneurysms with the whole view and magnified view at aneurysm site. *p < 0.01 by Fisher exact test; **p < 0.005 by log-rank test.

  8. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes

      Arun Pandian Chandrasekaran, Bharathi Suresh, Hyongbum (Henry) Kim, Kye-Seong Kim and Suresh Ramakrishna

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2446

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      Graphical Abstract

      Regulatory role of deubiquitinating enzymes in stem cell pluripotency and differentiation, cellular reprogramming and gametogenesis.

  9. Tissue-Specific Stem Cells

    1. Local CXCR4 Up-regulation in Injured Arterial Wall Contributes to Intimal Hyperplasia

      Xudong Shi, Lian-Wang Guo, Stephen Seedial, Toshio Takayama, Bowen Wang, Mengxue Zhang, Sarah R. Franco, Yi Si, Mirnal A Chaudhary, Bo Liu and K. Craig Kent

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2442

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      Graphic abstract

      A schematic model showing TGFβ/Smad3-stimulated CXCR4 expression in the vascular smooth muscle cell and its signaling activated by the SDF-1α ligand

  10. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. CXCR4 Signaling Negatively Modulates the Bipotential State of Hemogenic Endothelial Cells Derived from Embryonic Stem Cells by Attenuating the Endothelial Potential

      Tanzir Ahmed, Kiyomi Tsuji-Tamura and Minetaro Ogawa

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2441

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      Graphical Abstract

      ES cell-derived CD45- VE-cadherin+ CD41+ CXCR4+ cells represent a hemogenic endothelial cell (HEC) population. HECs encompass the differentiation programs for both the endothelial cell (EC) and hematopoietic cell (HC) lineages. A balance between these two programs provides an HEC with a bipotential state that allows the progeny of the cell to differentiate into both ECs and HCs. Fate of the bipotential HECs can be regulated by CXCL12/CXCR4 signaling, which suppresses the EC program independently of the hematopoietic fate.

  11. Cancer Stem Cells

    1. Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer

      Kung-Kai Kuo, King-Teh Lee, Ker-Kong Chen, Ya-Han Yang, Ying-Chu Lin, Ming-Ho Tsai, Kenly Wuputra, Yen-Liang Lee, Chia-Chen Ku, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Chun-Chieh Wu, Chee-Yin Chai, Richard Eckner, Chen-Lung Steve Lin, Sophie S-W Wang, Deng-Chyang Wu, Chang-Shen Lin and Kazunari K. Yokoyama

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2447

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      Graphical abstract

      The OCT4/c-JUN positive feedback loop found in reprogrammed HepG2-derived cancer stem cell-like cells (rG2-DC-1C) sheds light on the tumorigenesis of liver cancer. 4F, Yamanaka 4 factors; iPS-like cells, induced pluripotent stemlike cells.

  12. Tissue-Specific Stem Cells

    1. Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands

      Thomas J. Lynch, Preston J. Anderson, Weiliang Xie, Adrianne K. Crooke, Xiaoming Liu, Scott R. Tyler, Meihui Luo, David M Kusner, Yulong Zhang, Traci Neff, Daniel C. Burnette, Katherine S. Walters, Michael J. Goodheart, Kalpaj R. Parekh and John F. Engelhardt

      Accepted manuscript online: 24 JUN 2016 10:35AM EST | DOI: 10.1002/stem.2443

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      Graphical Abstract

      Two distinct stem cell (SC) compartments in the mouse trachea include basal cells in the surface airway epithelium (SAE) and submucosal glands (SMGs). This research demonstrates that SCs from these two compartments have unique and overlapping properties that respond to dynamic changes in Wnt signaling following injury. Slowly cycling label retaining (LRC) SCs isolated from the SMGs had a greater proliferative capacity than SAE LRCs and glandular LRCs reside near Wnt-active tubules. Isolated glandular SCs had a greater regenerative capacity to reconstitute a denuded tracheal xenograft than SAE SCs, and only glandular SCs formed gland-like clones in xenografts and organoid cultures.

  13. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. A Novel role for miR-1305 in Regulation of Pluripotency-Differentiation Balance, Cell Cycle and Apoptosis in Human Pluripotent Stem Cells

      Shibo Jin, Joseph Collin, Lili Zhu, David Montaner, Lyle Armstrong, Irina Neganova and Majlinda Lako

      Accepted manuscript online: 24 JUN 2016 03:31AM EST | DOI: 10.1002/stem.2444

  14. Tissue-Specific Stem Cells

    1. CXCR4+CD45- cells are niche forming for osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 signaling pathways in bone marrow

      Yoh Goto, Mineyoshi Aoyama, Takeo Sekiya, Hiroki Kakita, Yuko Waguri-Nagaya, Ken Miyazawa, Kiyofumi Asai and Shigemi Goto

      Accepted manuscript online: 24 JUN 2016 03:31AM EST | DOI: 10.1002/stem.2440

  15. Regenerative Medicine

    1. Glycoengineering of E-selectin ligands by intracellular versus extracellular fucosylation differentially affects osteotropism of human mesenchymal stem cells

      Brad Dykstra, Jungmin Lee, Luke J. Mortensen, Haixiao Yu, Zhengliang L. Wu, Charles P. Lin, Derrick J. Rossi and Robert Sackstein

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2435

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      Two complimentary approaches were used to create E-selectin ligands on human mesenchymal stem cells (MSC) using fucosyltransferase VI (FTVI): extracellularly, by treating cells with purified FTVI enzyme, and intracellularly, by transfecting cells with FTVI-encoding modified mRNA. The extent to which the newly created E-selectin ligands could improve MSC homing to bone was tested using in vivo calvarial imaging. This three-dimensional reconstruction of a xenotransplanted mouse calvarium region shows bone (grey) and blood vessels (red), 24 hours after intravenously co-transplanting fucosylated MSCs (blue) and control MSCs (green). Both fucosylation approaches significantly increased homing of MSCs to the bone marrow, but intracellularly fucosylated (FUT6-mod) MSCs demonstrated increased extravasation into bone marrow parenchyma compared to their exofucosylated counterparts (FTVI-exo). The observed differential biologic effects of FTVI activity in these two contexts may yield new strategies for improving the efficacy of human MSCs in clinical applications. **p<0.01.

  16. Translational and Clinical Research

    1. Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

      Wei Yao, Evan Yu-An Lay, Alexander Kot, Ruiwu Liu, Hongliang Zhang, Haiyan Chen, Kit Lam and Nancy E. Lane

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2433

  17. Regenerative Medicine

    1. HucMSC Exosome-Delivered 14-3-3ζ Orchestrates Self-control of the Wnt Response via Modulation of YAP during Cutaneous Regeneration

      Bin Zhang, Yinghong Shi, Aihua Gong, Zhaoji Pan, Hui Shi, Huan Yang, Hailong Fu, Yongmin Yan, Xu Zhang, Mei Wang, Wei Zhu, Hui Qian and Wenrong Xu

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2432

  18. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Screening of Human cDNA Library Reveals Two Differentiation-related Genes, HHEX and HLX, as Promoters of Early Phase Reprogramming Toward Pluripotency

      Tatsuya Yamakawa, Yoshiko Sato, Yasuko Matsumura, Yukiko Kobayashi, Yoshifumi Kawamura, Naoki Goshima, Shinya Yamanaka and Keisuke Okita

      Accepted manuscript online: 22 JUN 2016 07:01PM EST | DOI: 10.1002/stem.2436

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      We used a new screening strategy that investigated the effects of genes from a human cDNA library on reprogramming and discovered two genes, HHEX and HLX, which may offer new understanding on the induction of pluripotency. This article is protected by copyright.

  19. Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics

    1. Inhibition of lncRNA MIR31HG Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells

      Chanyuan Jin, Lingfei Jia, Yiping Huang, Yunfei Zheng, Ning Du, Yunsong Liu and Yongsheng Zhou

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2439

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      Schematic of the regulatory circuitry of MIR31HG and NF-κB. Under TNF-α and IL-17 stimulation, MIR31HG directly binds to IκBα and contributes to IκBα phosphorylation and NF-κB activation. The nuclear translocation of NF-κB in turn binds to MIR31HG promoter, upregulates its expression, and promotes its export to the cytoplasm where it exerts its function.

  20. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-cell Adhesion

      Jie Liu, Yanmei Qi, Shaohua Li, Shu-Chan Hsu, Siavash Saadat, June Hsu, Saum A. Rahimi, Leonard Y. Lee, Chenghui Yan, Xiaoxiang Tian and Yanling Han

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2434

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      Schematic model for a role of CREG1 in the formation of intercalated discs between cardiomyocytes. During cardiomyocyte differentiation from embryonic stem cells, CREG1 is upregulated and binds to Sec8 of the exocyst complex. The CREG1-exocyst interaction increases the delivery of N-cadherin from intracellular compartments, such as Golgi and recycling endosomes (ER), to the cell-cell adhesion sites, thereby promoting the formation of intercalated discs.

  21. Regenerative Medicine

    1. Generation of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration

      Jian-Yong Xu, Yee-Ki Lee, Xinru Ran, Song-Yan Liao, Jiayin Yang, Ka-Wing Au, Wing-Hon Lai, Miguel A Esteban and Hung-Fat Tse

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2438

    2. You have full text access to this OnlineOpen article
      TGF-β-expressing Mesenchymal Stem Cells Induce Local Tolerance in a Rat Liver Transplantation Model of Acute Rejection

      Jincao Tang, Renjie Yang, Ling Lv, Aihua Yao, Liyong Pu, Aihong Yin, Xiangcheng Li, Yue Yu, Scott L. Nyberg and Xuehao Wang

      Accepted manuscript online: 22 JUN 2016 07:00PM EST | DOI: 10.1002/stem.2437

  22. Tissue-Specific Stem Cells

    1. Cytoarchitecture, Proliferative Activity and Neuroblast Migration in the Subventricular Zone and Lateral Ventricle Extension of the Adult Guinea Pig Brain

      Nery Jara, Manuel Cifuentes, Fernando Martínez, Katterine Salazar and Francisco Nualart

      Accepted manuscript online: 14 JUN 2016 10:56AM EST | DOI: 10.1002/stem.2430

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      Graphical Abstract

      Schematic summary of the cellular composition of the subventricular zone and lateral ventricle extension (LVE) of the adult guinea pig brain. In the adult guinea pig brain, a narrow ventricular cavity connects the SVZ with the OB, similar to the LVE previously described in the adult human brain. In the guinea pig brain, ependymal cells line the LV and also LVE; neuroblasts are located in the subependymal area, but mostly along the LVE; proliferating BrdU + cells are mainly found in the SVZ; however, they are also found in LVE. Astrocytes are co-distributed with neuroblasts in the SVZ and surround the neuroblasts in LVE. Finally, in the guinea pig brain the LVE has a reduced proliferative activity; however, it works as a continuous pathway for neuroblasts migration to the OB.

  23. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. The Anterior-Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt- and BMP-Signaling

      Claudia Davenport, Ulf Diekmann, Insa Budde, Nora Detering and Ortwin Naujok

      Accepted manuscript online: 14 JUN 2016 10:51AM EST | DOI: 10.1002/stem.2428

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      Graphical abstract

      Differentiation of pluripotent stem cells (PSC) via the definitive endoderm (DE) germ layer into the patterned primitive gut tube (PGT). The anterior-posterior axis of the PGT is controlled by differential signaling of Wnt/beta-catenin-, BMP-, FGF- and retinoic acid signaling. BMP inhibition (BMPi) and to a lesser Wnt/beta-catenin inhibition (WNTi) induce a foregut-like SOX2-positive state. Active Wnt/beta-catenin supported by BMPs, FGFs and all-trans retinoic acid (ATRA) induce a hindgut-like state. SOX2 is strongly expressed in PSCs, becomes down regulated during endoderm commitment, and reappears in the foregut domain upon A-P patterning, whereas CDX2 is expressed in the hindgut domain. ATRA is able to posteriorize the foregut.

  24. Tissue-Specific Stem Cells

    1. Consecutive Alendronate Administration-Mediated Inhibition of Osteoclasts Improves Long-Term Engraftment Potential and Stress Resistance of HSCs

      Hyun-Jaung Sim, Sung-Ho Kook, Chi-Young Yun, Govinda Bhattarai, Eui-Sic Cho and Jeong-Chae Lee

      Accepted manuscript online: 14 JUN 2016 10:50AM EST | DOI: 10.1002/stem.2425

    2. Spla2-IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induce Differentiation Mediated through Enhanced JNK/C-Jun Activation

      Rahul M Sarate, Gopal L Chovatiya, Vagisha Ravi, Bharat Khade, Sanjay Gupta and Sanjeev K Waghmare

      Accepted manuscript online: 14 JUN 2016 10:47AM EST | DOI: 10.1002/stem.2418

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      Graphical Abstract:

      Overexpression of sPLA2-IIA in mice epidermis leads to hyperplasia of both interfollicular epidermis and sebaceous gland, with enlarged size of the junctional zone and dermal papillae. In addition, loss of self-renewal in hair follicle stem cells was due to increased proliferation and differentiation, mediated through increased level of mitogenic signaling followed by enhanced expression of c-Jun, FosB and Nr4a1.

    3. Characterisation of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming

      C Eguizabal, L Herrera, L de Oñate, N Montserrat, P Hajkova and JC Izpisua Belmonte

      Accepted manuscript online: 14 JUN 2016 10:46AM EST | DOI: 10.1002/stem.2422

    4. Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-β1

      Pedro Barcellos-de-Souza, Giuseppina Comito, Coral Pons-Segura, Maria Letizia Taddei, Valentina Gori, Valentina Becherucci, Franco Bambi, Francesca Margheri, Anna Laurenzana, Mario Del Rosso and Paola Chiarugi

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2412

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      Prostate carcinoma microenvironment recruits and activates mesenchymal stem cells into CAF via TGF-β1.

      TGF-β 1 produced by prostate carcinoma (PCa) cells and tumor-associated fibroblasts and macrophages is important in bone marrow-derived mesenchymal stem cells (BM-MSC) recruitment to PCa site and further transdifferentiation to the carcinoma-associated fibroblast (CAF)-like phenotype. CAF-like MSC promote PCa cells invasiveness, perform vascular mimicry abilities and recruit monocytes, which can further polarize into M2-like macrophages.

  25. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. Regulation of WNT Signaling by VSX2 during Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells

      Elizabeth E Capowski, Lynda S Wright, Kun Liang, M. Joseph Phillips, Kyle Wallace, Anna Petelinsek, Anna Hagstrom, Isabel Pinilla, Katarzyna Borys, Jessica Lien, Jee Hong Min, Sunduz Keles, James A Thomson and David M Gamm

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2414

  26. Translational and Clinical Research

    1. Cryopreserved MSCs are Susceptible to T-cell Mediated Apoptosis which is partly Rescued by IFNγ Licensing

      Raghavan Chinnadurai, Ian B Copland, Marco A Garcia, Christopher T Petersen, Christopher N Lewis, Edmund K Waller, Allan D Kirk and Jacques Galipeau

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2415

  27. Tissue-Specific Stem Cells

    1. Loss of Sfrp2 in the Niche Amplifies Stress-Induced Cellular Responses, and Impairs the in Vivo Regeneration of the Hematopoietic Stem Cell Pool

      Franziska Ruf, Christina Schreck, Alina Wagner, Sandra Grziwok, Charlotta Pagel, Sandra Romero, Matthias Kieslinger, Christian Peschel, Katharina S. Götze, Rouzanna Istvanffy and Robert A.J Oostendorp

      Accepted manuscript online: 14 JUN 2016 10:42AM EST | DOI: 10.1002/stem.2416

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      Hematopoietic stress (co-culture, regeneration, genotoxicity, and aging) results in reduced hematopoietic stem cell (HSC) numbers and quality. Here, we show that stromal Sfrp2 dampens the response of HSC to different forms of stress in vitro (co-cultures) and in vivo (regeneration, genotoxic insult, and aging). Without Sfrp2 (right hand figure), the niche's ability to limit the stress response is diminished. As a result, HSC activated from quiescence (qHSC) into an activated state (aHSC) show an amplified stress response with an increased DNA damage response. In this Sfrp2-deficient environment, aHSC do not self-renew efficiently, which results in a defective regeneration of the HSC pool. Thus, Sfrp2 secreted by the niche preserves the number of HSCs, a finding which may help to identify new ways to prevent the loss of stem cells under stress conditions.

  28. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    1. You have free access to this content
      Measuring physiological responses of human pluripotent stem cell derived cardiomyocytes to drugs and disease

      Berend J. van Meer, Leon G.J. Tertoolen and Christine L. Mummery

      Accepted manuscript online: 2 JUN 2016 03:30AM EST | DOI: 10.1002/stem.2403

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      Measuring pluripotent stem cell derived cardiomyocyte physiology

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