Stem Cells: A Renaissance in Human Biology Research

The understanding of human biology and how it relates to that of other species represents an ancient quest. Limited access to human material, particularly during early development, has restricted researchers to only scratching the surface of this inherently challenging subject. Recent technological innovations, such as single cell "omics" and human stem cell derivation, have now greatly accelerated our ability to gain insights into uniquely human biology. The opportunities afforded to delve molecularly into scarce material and to model human embryogenesis and pathophysiological processes are leading to new insights of human development and are changing our understanding of disease and choice of therapy options.

[1]  Mamoru Ito,et al.  Current advances in humanized mouse models , 2012, Cellular and Molecular Immunology.

[2]  Gail H Deutsch,et al.  In vitro generation of human pluripotent stem cell derived lung organoids , 2015, eLife.

[3]  George Q. Daley,et al.  Reprogramming of human somatic cells to pluripotency with defined factors , 2008, Nature.

[4]  J. Rossant,et al.  Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryos. , 2011, Developmental biology.

[5]  Qinghua Shi,et al.  Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro. , 2016, Cell stem cell.

[6]  Pei-Rong Wang,et al.  Targeting SOX17 in human embryonic stem cells creates unique strategies for isolating and analyzing developing endoderm. , 2011, Cell stem cell.

[7]  Juan Carlos Izpisua Belmonte,et al.  An alternative pluripotent state confers interspecies chimaeric competency , 2015, Nature.

[8]  Andrew J. Ewald,et al.  Three-dimensional organotypic culture: experimental models of mammalian biology and disease , 2014, Nature Reviews Molecular Cell Biology.

[9]  Hans Clevers,et al.  Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. , 2011, Gastroenterology.

[10]  S. Mitalipov,et al.  Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer , 2013, Cell.

[11]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[12]  K. Pollard,et al.  Genomic approaches to studying human-specific developmental traits , 2015, Development.

[13]  P. Tesar Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Mollenkopf,et al.  A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro , 2014, Gut.

[15]  A. Brunet,et al.  Epigenetic regulation of aging stem cells , 2011, Oncogene.

[16]  H. Ohta,et al.  A Signaling Principle for the Specification of the Germ Cell Lineage in Mice , 2009, Cell.

[17]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors , 2008 .

[18]  R. Pijnenborg,et al.  The role of invasive trophoblast in implantation and placentation of primates , 2015, Philosophical Transactions of the Royal Society B: Biological Sciences.

[19]  F. Tang,et al.  The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells , 2015, Cell.

[20]  Y. Sasai Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. , 2013, Cell stem cell.

[21]  H. Van de Velde,et al.  Totipotency and lineage segregation in the human embryo. , 2014, Molecular human reproduction.

[22]  Robert Lanza,et al.  Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres , 2006, Nature.

[23]  T. O’Leary,et al.  Treatment of human embryos with the TGFβ inhibitor SB431542 increases epiblast proliferation and permits successful human embryonic stem cell derivation. , 2014, Human reproduction.

[24]  S. Horvath,et al.  Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing , 2013, Nature.

[25]  Jun Wu,et al.  Stem cells: A designer's guide to pluripotency , 2014, Nature.

[26]  M. Azim Surani,et al.  Blimp1 is a critical determinant of the germ cell lineage in mice , 2005, Nature.

[27]  Jun Wu,et al.  The Molecular Harbingers of Early Mammalian Embryo Patterning , 2016, Cell.

[28]  Valeria Orlova,et al.  Complex Tissue and Disease Modeling using hiPSCs. , 2016, Cell stem cell.

[29]  Y. Yashiro‐Ohtani,et al.  The expression of Sox17 identifies and regulates haemogenic endothelium , 2013, Nature Cell Biology.

[30]  R. Pedersen,et al.  Human-Mouse Chimerism Validates Human Stem Cell Pluripotency , 2016, Cell stem cell.

[31]  Chad A. Cowan,et al.  Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines. , 2009, Cell stem cell.

[32]  John W Haycock,et al.  3D cell culture: a review of current approaches and techniques. , 2011, Methods in molecular biology.

[33]  M. Spector,et al.  Organoid Models of Human and Mouse Ductal Pancreatic Cancer , 2015, Cell.

[34]  V. Wilson,et al.  In Vivo differentiation potential of epiblast stem cells revealed by chimeric embryo formation. , 2012, Cell reports.

[35]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[36]  Nick Barker,et al.  Organoids as an in vitro model of human development and disease , 2016, Nature Cell Biology.

[37]  V. Tabar,et al.  Pluripotent stem cells in regenerative medicine: challenges and recent progress , 2014, Nature Reviews Genetics.

[38]  Madeline A. Lancaster,et al.  Cerebral organoids model human brain development and microcephaly , 2013, Nature.

[39]  R. McKay,et al.  New cell lines from mouse epiblast share defining features with human embryonic stem cells , 2007, Nature.

[40]  Luke A. Gilbert,et al.  Engineering Complex Synthetic Transcriptional Programs with CRISPR RNA Scaffolds , 2015, Cell.

[41]  H. Ohta,et al.  Offspring from Oocytes Derived from in Vitro Primordial Germ Cell–like Cells in Mice , 2012, Science.

[42]  G. Martin,et al.  Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Yoshiki Sasai,et al.  Cytosystems dynamics in self-organization of tissue architecture , 2013, Nature.

[44]  K. Zhang,et al.  DNA Demethylation Dynamics in the Human Prenatal Germline , 2015, Cell.

[45]  M. Wiles,et al.  Generation of improved humanized mouse models for human infectious diseases , 2014, Journal of Immunological Methods.

[46]  J. Nichols,et al.  Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines. , 2001, Development.

[47]  R. DePinho,et al.  Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a , 2006, Nature.

[48]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[49]  Robert G. Parton,et al.  Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis , 2016, Nature.

[50]  Hideshi Kawakami,et al.  Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. , 2015, Cell reports.

[51]  Janet Rossant,et al.  Mouse and human blastocyst-derived stem cells: vive les differences , 2015, Development.

[52]  Hans Clevers,et al.  In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. , 2015, Gastroenterology.

[53]  H. Van de Velde,et al.  The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos , 2012, Development.

[54]  H. Van de Velde,et al.  WNT3 and membrane-associated β-catenin regulate trophectoderm lineage differentiation in human blastocysts. , 2015, Molecular human reproduction.

[55]  M. Surani,et al.  Human Germline: A New Research Frontier , 2015, Stem cell reports.

[56]  Holm Zaehres,et al.  LIF/STAT3 Signaling Fails to Maintain Self‐Renewal of Human Embryonic Stem Cells , 2004, Stem cells.

[57]  A. Wagers,et al.  Stem cell aging: mechanisms, regulators and therapeutic opportunities , 2014, Nature Medicine.

[58]  Yoshiki Sasai,et al.  Self-formation of optic cups and storable stratified neural retina from human ESCs. , 2012, Cell stem cell.

[59]  Kole T. Roybal,et al.  Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits , 2016, Cell.

[60]  T. Down,et al.  Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine , 2013, Science.

[61]  J. Nichols,et al.  Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis , 2015, Developmental cell.

[62]  M. Surani,et al.  Regulatory principles of pluripotency: from the ground state up. , 2014, Cell stem cell.

[63]  R. Martienssen,et al.  Transgenerational Epigenetic Inheritance: Myths and Mechanisms , 2014, Cell.

[64]  M. Asashima,et al.  Generation of stomach tissue from mouse embryonic stem cells , 2015, Nature Cell Biology.

[65]  J. Rossant,et al.  Mouse embryonic chimeras: tools for studying mammalian development , 2003, Development.

[66]  Kevin Eggan,et al.  Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. , 2013, Developmental biology.

[67]  Hans Clevers,et al.  Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. , 2013, Cell stem cell.

[68]  J. Nichols,et al.  The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification , 2014, Nature Cell Biology.

[69]  I. Amit,et al.  Derivation of novel human ground state naive pluripotent stem cells , 2013, Nature.

[70]  J. Rossant Human embryology: Implantation barrier overcome , 2016, Nature.

[71]  E. Cuppen,et al.  Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures , 2014, Cell.

[72]  B. Stanger,et al.  Facultative stem cells in liver and pancreas: Fact and fancy , 2011, Developmental dynamics : an official publication of the American Association of Anatomists.

[73]  Kay Elder,et al.  Defining the three cell lineages of the human blastocyst by single-cell RNA-seq , 2015, Development.

[74]  I. Weissman,et al.  Hematopoietic Stem Cell Quiescence Attenuates DNA Damage Response and Permits DNA Damage Accumulation During Aging , 2007, Cell cycle.

[75]  K. Niakan,et al.  Human pre-implantation embryo development , 2012, Development.

[76]  J. Nichols,et al.  Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human , 2014, Cell.

[77]  Ashley R Bonneau,et al.  Zygotic genome activation during the maternal-to-zygotic transition. , 2014, Annual review of cell and developmental biology.

[78]  Aviv Regev,et al.  DNA methylation dynamics of the human preimplantation embryo , 2014, Nature.

[79]  M. Gerstein,et al.  FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders , 2015, Cell.

[80]  Jun Wu,et al.  Interspecies chimeric complementation for the generation of functional human tissues and organs in large animal hosts , 2016, Transgenic Research.

[81]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[82]  K. Kurimoto,et al.  Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. , 2008, Genes & development.

[83]  Hans Clevers,et al.  Organoid Cultures Derived from Patients with Advanced Prostate Cancer , 2014, Cell.

[84]  Samit R. Joshi,et al.  Aging of the innate immune system. , 2010, Current opinion in immunology.

[85]  Kiho Lee Zygotic Genome Activation , 2017, Methods in Molecular Biology.

[86]  R. Prather,et al.  Genetically engineered pig models for human diseases. , 2013, Annual review of animal biosciences.

[87]  F. Tang,et al.  The DNA methylation landscape of human early embryos , 2014, Nature.

[88]  K. Shirahige,et al.  A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. , 2013, Developmental cell.

[89]  T. Kirkwood,et al.  Understanding the Odd Science of Aging , 2005, Cell.

[90]  J. Nichols,et al.  Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass , 2016, Stem cell reports.

[91]  H. Yonekawa,et al.  Evidence for crucial role of hindgut expansion in directing proper migration of primordial germ cells in mouse early embryogenesis. , 2009, Developmental biology.

[92]  M. Azim Surani,et al.  A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development , 2015, Cell.

[93]  Alvaro Plaza Reyes,et al.  Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos , 2016, Cell.

[94]  J. Nichols,et al.  Human hypoblast formation is not dependent on FGF signalling , 2012, Developmental biology.

[95]  J. Nichols,et al.  Naive and primed pluripotent states. , 2009, Cell stem cell.

[96]  R. Passier,et al.  Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells , 2015, Development.

[97]  M. Surani,et al.  Epigenetic reprogramming in mouse primordial germ cells , 2002, Mechanisms of Development.

[98]  Tony Pawson,et al.  Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. , 2006, Developmental cell.

[99]  Hans Clevers,et al.  A functional CFTR assay using primary cystic fibrosis intestinal organoids , 2013, Nature Medicine.

[100]  D. Gifford,et al.  Differentiated human stem cells resemble fetal, not adult, β cells , 2014, Proceedings of the National Academy of Sciences.

[101]  H. Ohta,et al.  Induction of mouse germ-cell fate by transcription factors in vitro , 2013, Nature.

[102]  T. O’Leary,et al.  The combination of inhibitors of FGF/MEK/Erk and GSK3β signaling increases the number of OCT3/4- and NANOG-positive cells in the human inner cell mass, but does not improve stem cell derivation. , 2013, Stem cells and development.

[103]  I. Weissman,et al.  The aging of hematopoietic stem cells , 1996, Nature Medicine.

[104]  J. I. Izpisúa Belmonte,et al.  Dynamic Pluripotent Stem Cell States and Their Applications. , 2015, Cell stem cell.

[105]  O. Klein,et al.  Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo , 2015, Stem cell reports.

[106]  Benjamin S. Freedman,et al.  Nephron organoids derived from human pluripotent stem cells model kidney development and injury , 2015, Nature Biotechnology.

[107]  M. Azim Surani,et al.  SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate , 2015, Cell.

[108]  Hans Clevers,et al.  Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver , 2015, Cell.

[109]  S. Yamanaka,et al.  Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells. , 2015, Cell stem cell.

[110]  Michael Schumacher,et al.  Modeling human development and disease in pluripotent stem cell-derived gastric organoids , 2014, Nature.

[111]  S. Bodovitz,et al.  Single cell analysis: the new frontier in 'omics'. , 2010, Trends in biotechnology.

[112]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[113]  A. Brivanlou,et al.  Self-organization of the in vitro attached human embryo , 2016, Nature.

[114]  Takanori Kanai,et al.  Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids , 2015, Nature Medicine.

[115]  Russell M. Gordley,et al.  Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors , 2016, Cell.

[116]  J. Hanna,et al.  Dynamic stem cell states: naive to primed pluripotency in rodents and humans , 2016, Nature Reviews Molecular Cell Biology.

[117]  Jun Wu,et al.  Metabolic exit from naive pluripotency , 2015, Nature Cell Biology.

[118]  Linda G. Griffith,et al.  Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6 , 2016, Nature Communications.

[119]  R. Jaenisch,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2007, Nature.

[120]  Angelique M. Nelson,et al.  Derivation of naïve human embryonic stem cells , 2014, Proceedings of the National Academy of Sciences.

[121]  Mark M. Davis,et al.  The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse , 2005, Development.

[122]  R. Young,et al.  Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency , 2014, Cell stem cell.

[123]  Ruiqiang Li,et al.  Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells , 2013, Nature Structural &Molecular Biology.

[124]  Elizabeth E. Hoskins,et al.  Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro , 2010, Nature.

[125]  Ferdinand von Meyenn,et al.  Forget the Parents: Epigenetic Reprogramming in Human Germ Cells , 2015, Cell.

[126]  Juergen A. Knoblich,et al.  Organogenesis in a dish: Modeling development and disease using organoid technologies , 2014, Science.

[127]  Adam A. Margolin,et al.  The metabolome regulates the epigenetic landscape during naïve to primed human embryonic stem cell transition , 2015, Nature Cell Biology.

[128]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[129]  J. Rossant,et al.  Developmental differences in the expression of FGF receptors between human and mouse embryos. , 2014, Placenta.

[130]  M. Suyama,et al.  Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development , 2014, PLoS genetics.

[131]  A. Consiglio,et al.  Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes , 2008, Nature Biotechnology.

[132]  M. Trotter,et al.  Derivation of pluripotent epiblast stem cells from mammalian embryos , 2007, Nature.

[133]  M. Zernicka-Goetz,et al.  The Acquisition of Cell Fate in Mouse Development: How Do Cells First Become Heterogeneous? , 2016, Current topics in developmental biology.

[134]  Gayle M. Smythe,et al.  Notch-Mediated Restoration of Regenerative Potential to Aged Muscle , 2003, Science.

[135]  J. Nichols,et al.  Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human , 2014, Cell.

[136]  Bon-Kyoung Koo,et al.  Modeling mouse and human development using organoid cultures , 2015, Development.

[137]  W. Reik,et al.  The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells , 2012, Molecular cell.

[138]  James E. DiCarlo,et al.  RNA-Guided Human Genome Engineering via Cas9 , 2013, Science.

[139]  G. Fan,et al.  The naive state of human pluripotent stem cells: a synthesis of stem cell and preimplantation embryo transcriptome analyses. , 2014, Cell stem cell.

[140]  R. McKay,et al.  Epiblast stem cells contribute new insight into pluripotency and gastrulation , 2010, Development, growth & differentiation.

[141]  Yutaka Suzuki,et al.  High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice , 2013, Genome research.

[142]  Janet Rossant,et al.  Cell and molecular regulation of the mouse blastocyst , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[143]  K. Niakan,et al.  Self-organisation of the human embryo in the absence of maternal tissues , 2016, Nature Cell Biology.

[144]  H. Ohta,et al.  Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells , 2011, Cell.