The Experts below are selected from a list of 31614 Experts worldwide ranked by ideXlab platform

Irving L Weissman - One of the best experts on this subject based on the ideXlab platform.

  • clonal origins of the hematopoietic syStem the single most elegant experiment
    Journal of Immunology, 2014
    Co-Authors: Irving L Weissman
    Abstract:

    The paper by Becker et al. ([1][1]) is the single most beautiful paper I have read. It follows what, in my view, is the most important single paper to the communities of immunology, hematopoiesis, and Stem Cell Biology by Ray Owen in 1945 ([2][2]). This paper established that hematopoietic

  • A neurosurgeon's guide to Stem Cells, cancer Stem Cells, and brain tumor Stem Cells.
    Neurosurgery, 2009
    Co-Authors: Samuel H. Cheshier, M. Yashar S. Kalani, Michael Lim, Laurie Ailles, Steven L. Huhn, Irving L Weissman
    Abstract:

    Stem Cells and their potential applications have become the forefront of scientific, political, and ethical discourse. Whereas Stem Cells were long accepted as units of development and evolution, it is now becoming increasingly clear that they are also units of oncogenesis. Although the field of Stem Cell Biology is expanding at an astounding rate, the data attained are not readily translatable for the physicians who may eventually deliver these tools to patients. Herein, we provide a brief review of Stem Cell and cancer Stem Cell Biology and highlight the scientific and clinical implications of recent findings regarding the presence of cancer-forming Stem Cells in brain tumors.

  • Hematopoietic Stem Cells: the paradigmatic tissue-specific Stem Cell
    American Journal of Pathology, 2006
    Co-Authors: David Bryder, Derrick J Rossi, Irving L Weissman
    Abstract:

    The recent prospective isolation of a wide variety of somatically derived Stem Cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-specific Stem and progenitor Cells and fueled enthusiasm for the use of such Cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic Stem Cells (HSCs) are arguably the most well-characterized tissue-specific Stem Cell, with decades of basic research and clinical application providing not only a profound understanding of the principles of Stem Cell Biology, but also of its potential pitfalls. It is our belief that emerging Stem Cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding Stem Cell Biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for Stem Cell Biology.

  • biological perspectives hematopoietic Stem Cells the paradigmatic tissue specific Stem Cell
    2006
    Co-Authors: David Bryder, Derrick J Rossi, Irving L Weissman
    Abstract:

    The recent prospective isolation of a wide variety of somatically derived Stem Cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-specific Stem and progenitor Cells and fueled enthusiasm for the use of such Cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic Stem Cells (HSCs) are arguably the most well-characterized tissue-specific Stem Cell , with decades of basic research and clinical application providing not only a profound understanding of the principles of Stem Cell Biology, but also of its potential pitfalls. It is our belief that emerging Stem Cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding Stem Cell Biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for Stem Cell Biology. (Am J Pathol 2006, 169:338–346; DOI: 10.2353/ajpath.2006.060312)

Sheng Ding - One of the best experts on this subject based on the ideXlab platform.

  • translational strategies and challenges in regenerative medicine
    Nature Medicine, 2014
    Co-Authors: Stefanie Dimmele, Sheng Ding, Thomas A Rando, Ala O Trounso
    Abstract:

    Our understanding of Stem Cell Biology is increasing, but the translation of this knowledge into regenerative medicine therapies for aged or diseased tissues is proving challenging. In this Perspective, four experts in the field discuss strategies for overcoming the major hurdles facing the translational regenerative field.

  • chemical approaches to Stem Cell Biology and therapeutics
    Cell Stem Cell, 2013
    Co-Authors: Wanguo Wei, Sheng Ding
    Abstract:

    Small molecules that modulate Stem Cell fate and function offer significant opportunities that will allow the full realization of the therapeutic potential of Stem Cells. Rational design and screening for small molecules have identified useful compounds to probe fundamental mechanisms of Stem Cell self-renewal, differentiation, and reprogramming and have facilitated the development of Cell-based therapies and therapeutic drugs targeting endogenous Stem and progenitor Cells for repair and regeneration. Here, we will discuss recent scientific and therapeutic progress, as well as new perspectives and future challenges for using chemical approaches in Stem Cell Biology and regenerative medicine.

  • concise review a chemical approach to control Cell fate and function
    Stem Cells, 2012
    Co-Authors: Kai Jiang, Sheng Ding
    Abstract:

    Stem Cells are essential for maintaining tissue homeostasis and mediating physiological and pathological regeneration. Recent breakthroughs in Stem Cell Biology have generated tremendous enthusiasm and hope for the therapeutic potential of Stem Cells in regenerative medicine. However, this research is still in an early development stage. An improved understanding of Stem Cell Biology is required to precisely manipulate Stem Cell fate and to harness these Cells for regenerative medicine. Small molecules, targeting specific signaling pathways and mechanisms, are powerful tools for manipulating Stem Cells for desired outcomes. Those small molecules are increasingly important in probing the fundamental mechanisms of Stem Cell Biology and facilitating the development of therapeutic approaches for regenerative medicine. These could involve Cell replacement therapies with homogenous functional Cells produced under chemically defined conditions in vitro and the development of small-molecule drugs that modulate patient's endogenous Cells for therapeutic benefit.

  • chemical strategies for Stem Cell Biology and regenerative medicine
    Annual Review of Biomedical Engineering, 2011
    Co-Authors: Saiyong Zhu, Wanguo Wei, Sheng Ding
    Abstract:

    Stem Cell technology holds great promises for the cures of devastating diseases, injuries, aging, and even cancers as it is applied in regenerative medicine. Recent breakthroughs in the development of induced pluripotent Stem Cell techniques and efficient differentiation strategies have generated tremendous enthusiasm and efforts to explore the therapeutic potential of Stem Cells. Small molecules, which target specific signaling pathways and/or proteins, have been demonstrated to be particularly valuable for manipulating Cell fate, state, and function. Such small molecules not only are useful in generating desired Cell types in vitro for various applications but also could be further developed as conventional therapeutics to stimulate patients' endogenous Cells to repair and regenerate in vivo. Here, we focus on recent progress in the use of small molecules in Stem Cell Biology and regenerative medicine.

  • small molecules that modulate embryonic Stem Cell fate and somatic Cell reprogramming
    Trends in Pharmacological Sciences, 2010
    Co-Authors: Wenlin Li, Sheng Ding
    Abstract:

    Recent breakthroughs in Stem Cell Biology, especially the development of induced pluripotent Stem Cell technique, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of Stem Cells in regenerative medicine. Improved understanding of Stem Cell Biology, in addition to better control of Stem Cell fate, is critical to realize this potential. Small molecules, targeting specific signaling pathways and/or mechanisms, have been shown to be useful chemical tools in manipulating Cell fate, state and function. These small molecules are starting to play increasingly important roles in both elucidating the fundamental Biology of Stem Cells and facilitating the development of therapeutic approaches toward regenerative medicine. Such approaches could involve Cell replacement therapies using homogenous functional Cells produced under chemically defined conditions in vitro and the development of small-molecule drugs that can stimulate patients' endogenous Cells to repair and regenerate. Here, we review recent progress in using small molecules to sustain pluripotency, or induce differentiation of embryonic Stem Cells. We also highlight small molecules that can replace transcription factors and/or enhance efficiency during somatic Cell reprogramming.

Hongchao Guo - One of the best experts on this subject based on the ideXlab platform.

  • applications of genetically engineered human pluripotent Stem Cell reporters in cardiac Stem Cell Biology
    Current Opinion in Biotechnology, 2018
    Co-Authors: Joe Z Zhang, Hongchao Guo
    Abstract:

    The advent of human pluripotent Stem Cells (hPSCs) has benefited many fields, from regenerative medicine to disease modeling, with an especially profound effect in cardiac research. Coupled with other novel technologies in genome engineering, hPSCs offer a great opportunity to delineate human cardiac lineages, investigate inherited cardiovascular diseases, and assess the safety and efficacy of Cell-based therapies. In this review, we provide an overview of methods for generating genetically engineered hPSC reporters and a succinct synopsis of a variety of hPSC reporters, with a particular focus on their applications in cardiac Stem Cell Biology.

Satish K Nandakumar - One of the best experts on this subject based on the ideXlab platform.

  • 2002 genetic predisposition to myeloproliferative neoplasms implicates hematopoietic Stem Cell Biology
    Experimental Hematology, 2020
    Co-Authors: Erik L Bao, Satish K Nandakumar, Xiaotian Liao, Alexander G Bick, Juha Karjalainen, Aarno Palotie, John E Dick, Pradeep Natarajan, Michael Milyavsky
    Abstract:

    Inherited genetic variants substantially contribute to the risk of myeloproliferative neoplasms (MPNs), a type of blood cancer that arise in the hematopoietic Stem Cell (HSC) compartment. To identify the germline genetic factors and underlying mechanisms predisposing to MPNs, we conducted a genome-wide association study involving 3,797 MPN cases and 1,152,977 controls and identified 17 genome-wide significant loci. We find an enrichment for risk variants mapping to accessible chromatin in HSCs, an association between MPN risk and multi-lineage blood Cell traits, an association with longer leukocyte telomere length, and a significant genetic correlation with predisposition to clonal hematopoiesis of indeterminate potential. Collectively, all of these findings implicate HSC function and self-renewal. In addition to these global studies, we performed in depth mechanistic studies at one locus located ∼12kb downstream of the transcription factor GFI1B. Fine-mapping analyses and reporter assays identified rs524137 as the likely causal variant with the risk allele decreasing hematopoietic reporter activity. Endogenous deletion of the 1.6 kb enhancer region harboring this variant with Cas9 ribonucleoproteins in adult human hematopoietic Stem and progenitor Cells (HSPCs) resulted in ∼65% editing with a 36% reduction in GFI1B expression. Furthermore, deletion of GFI1B enhancer improved the maintenance of phenotypic HSCs during a 7-day HSPC culture and increased progenitor self-renewal capacity in colony replating assays. Interestingly, deletion of this enhancer only affected HSPC function without disruption of erythropoiesis, an independent effect observed with GFI1B coding perturbation. These results and our ongoing studies demonstrate that the GFI1B MPN risk locus expands HSPCs and reinforces this general mechanism as a risk factor for MPN acquisition.

  • genetic predisposition to myeloproliferative neoplasms implicates hematopoietic Stem Cell Biology
    bioRxiv, 2019
    Co-Authors: Erik L Bao, Satish K Nandakumar, Xiaotian Liao, Alexander G Bick, Juha Karjalainen, Marcin Tabaka
    Abstract:

    Myeloproliferative neoplasms (MPNs) are blood cancers characterized by excessive production of mature myeloid Cells that result from the acquisition of somatic driver mutations in hematopoietic Stem Cells (HSCs)1. While substantial progress has been made to define the causal somatic mutation profile for MPNs2, epidemiologic studies indicate a significant heritable component for the disease that is among the highest known for all cancers3. However, only a limited set of genetic risk loci have been identified, and the underlying biological mechanisms leading to MPN acquisition remain unexplained. Here, to define the inherited risk profile, we conducted the largest genome-wide association study of MPNs to date (978,913 individuals with 3,224 cases) and identified 14 genome-wide significant loci, as well as a polygenic signature that increases the odds for disease acquisition by nearly 3-fold between the top and median deciles. Interestingly, we find a shared genetic architecture between MPN risk and several hematopoietic traits spanning distinct lineages, as well as an association between increased MPN risk and longer leukocyte telomere length, collectively implicating HSC function and self-renewal. Strikingly, we find a significant enrichment for risk variants mapping to accessible chromatin in HSCs compared with other hematopoietic populations. Finally, gene mapping identifies modulators of HSC Biology and targeted variant-to-function analyses suggest likely roles for CHEK2 and GFI1B in altering HSC function to confer disease risk. Overall, we demonstrate the power of human genetic studies to illuminate a previously unappreciated mechanism for MPN risk through modulation of HSC function.

  • genetic predisposition to myeloproliferative neoplasms implicates hematopoietic Stem Cell Biology
    bioRxiv, 2019
    Co-Authors: Satish K Nandakumar, Xiaotian Liao, Alexander G Bick, Juha Karjalainen, Marcin Tabaka, Aki S Havulinna, Tuomo Kiiskinen
    Abstract:

    Myeloproliferative neoplasms (MPNs) are blood cancers characterized by excessive production of mature myeloid Cells that result from the acquisition of somatic driver mutations in hematopoietic Stem Cells (HSCs)1. While substantial progress has been made to define the causal somatic mutation profile for MPNs2, epidemiologic studies indicate a significant heritable component for the disease that is among the highest known for all cancers3. However, only a limited set of genetic risk loci have been identified, and the underlying biological mechanisms leading to MPN acquisition remain unexplained. Here, to define the inherited risk profile, we conducted the largest genome-wide association study of MPNs to date (978,913 individuals with 3,224 cases) and identified 14 genome-wide significant loci, as well as a polygenic signature that increases the odds for disease acquisition by nearly 3-fold between the top and median deciles. Interestingly, we find a shared genetic architecture between MPN risk and several hematopoietic traits spanning distinct lineages, as well as an association between increased MPN risk and longer leukocyte telomere length, collectively implicating HSC function and self-renewal. Strikingly, we find a significant enrichment for risk variants mapping to accessible chromatin in HSCs compared with other hematopoietic populations. Finally, gene mapping identifies modulators of HSC Biology and targeted variant-to-function analyses suggest likely roles for CHEK2 and GFI1B in altering HSC function to confer disease risk. Overall, we demonstrate the power of human genetic studies to illuminate a previously unappreciated mechanism for MPN risk through modulation of HSC function.

Fernando D. Camargo - One of the best experts on this subject based on the ideXlab platform.

  • the hippo signaling pathway and Stem Cell Biology
    Trends in Cell Biology, 2012
    Co-Authors: Azucena Ramos, Fernando D. Camargo
    Abstract:

    Stem Cell (SC) activity fluctuates throughout an organism's lifetime to maintain homeostatic conditions in all tissues. As animals develop and age, their organs must remodel and regenerate themselves in response to environmental and physiological demands. Recently, the highly conserved Hippo signaling pathway, discovered in Drosophila melanogaster , has been implicated as a key regulator of organ size control across species. Deregulation is associated with substantial overgrowth phenotypes and eventual onset of cancer in various tissues. Importantly, emerging evidence suggests that the Hippo pathway can modulate its effects on tissue size by the direct regulation of SC proliferation and maintenance. These findings provide an attractive model for how this pathway might communicate physiological needs for growth to tissue-specific SC pools. In this review, we summarize the current and emerging data linking Hippo signaling to SC function.