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https://www.readbyqxmd.com/read/28129541/interspecies-chimerism-with-mammalian-pluripotent-stem-cells
#1
Jun Wu, Aida Platero-Luengo, Masahiro Sakurai, Atsushi Sugawara, Maria Antonia Gil, Takayoshi Yamauchi, Keiichiro Suzuki, Yanina Soledad Bogliotti, Cristina Cuello, Mariana Morales Valencia, Daiji Okumura, Jingping Luo, Marcela Vilariño, Inmaculada Parrilla, Delia Alba Soto, Cristina A Martinez, Tomoaki Hishida, Sonia Sánchez-Bautista, M Llanos Martinez-Martinez, Huili Wang, Alicia Nohalez, Emi Aizawa, Paloma Martinez-Redondo, Alejandro Ocampo, Pradeep Reddy, Jordi Roca, Elizabeth A Maga, Concepcion Rodriguez Esteban, W Travis Berggren, Estrella Nuñez Delicado, Jeronimo Lajara, Isabel Guillen, Pedro Guillen, Josep M Campistol, Emilio A Martinez, Pablo Juan Ross, Juan Carlos Izpisua Belmonte
Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28045100/ground-rules-of-the-pluripotency-gene-regulatory-network
#2
REVIEW
Mo Li, Juan Carlos Izpisua Belmonte
Pluripotency is a state that exists transiently in the early embryo and, remarkably, can be recapitulated in vitro by deriving embryonic stem cells or by reprogramming somatic cells to become induced pluripotent stem cells. The state of pluripotency, which is stabilized by an interconnected network of pluripotency-associated genes, integrates external signals and exerts control over the decision between self-renewal and differentiation at the transcriptional, post-transcriptional and epigenetic levels. Recent evidence of alternative pluripotency states indicates the regulatory flexibility of this network...
March 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/27984723/in%C3%A2-vivo-amelioration-of-age-associated-hallmarks-by-partial-reprogramming
#3
Alejandro Ocampo, Pradeep Reddy, Paloma Martinez-Redondo, Aida Platero-Luengo, Fumiyuki Hatanaka, Tomoaki Hishida, Mo Li, David Lam, Masakazu Kurita, Ergin Beyret, Toshikazu Araoka, Eric Vazquez-Ferrer, David Donoso, Jose Luis Roman, Jinna Xu, Concepcion Rodriguez Esteban, Gabriel Nuñez, Estrella Nuñez Delicado, Josep M Campistol, Isabel Guillen, Pedro Guillen, Juan Carlos Izpisua Belmonte
Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27919073/mitochondrial-replacement-in-human-oocytes-carrying-pathogenic-mitochondrial-dna-mutations
#4
Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov
Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27918510/human-organs-from-animal-bodies
#5
Juan Carlos Izpisúa Belmonte
No abstract text is available yet for this article.
October 18, 2016: Scientific American
https://www.readbyqxmd.com/read/27905428/stem-cells-and-interspecies-chimaeras
#6
Jun Wu, Henry T Greely, Rudolf Jaenisch, Hiromitsu Nakauchi, Janet Rossant, Juan Carlos Izpisua Belmonte
Chimaeras are both monsters of the ancient imagination and a long-established research tool. Recent advances, particularly those dealing with the identification and generation of various kinds of stem cells, have broadened the repertoire and utility of mammalian interspecies chimaeras and carved out new paths towards understanding fundamental biology as well as potential clinical applications.
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27851729/in-vivo-genome-editing-via-crispr-cas9-mediated-homology-independent-targeted-integration
#7
Keiichiro Suzuki, Yuji Tsunekawa, Reyna Hernandez-Benitez, Jun Wu, Jie Zhu, Euiseok J Kim, Fumiyuki Hatanaka, Mako Yamamoto, Toshikazu Araoka, Zhe Li, Masakazu Kurita, Tomoaki Hishida, Mo Li, Emi Aizawa, Shicheng Guo, Song Chen, April Goebl, Rupa Devi Soligalla, Jing Qu, Tingshuai Jiang, Xin Fu, Maryam Jafari, Concepcion Rodriguez Esteban, W Travis Berggren, Jeronimo Lajara, Estrella Nuñez-Delicado, Pedro Guillen, Josep M Campistol, Fumio Matsuzaki, Guang-Hui Liu, Pierre Magistretti, Kun Zhang, Edward M Callaway, Kang Zhang, Juan Carlos Izpisua Belmonte
Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals)...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27777973/systems-biology-analysis-reveals-role-of-mdm2-in-diabetic-nephropathy
#8
Rintaro Saito, Anaïs Rocanin-Arjo, Young-Hyun You, Manjula Darshi, Benjamin Van Espen, Satoshi Miyamoto, Jessica Pham, Minya Pu, Simone Romoli, Loki Natarajan, Wenjun Ju, Matthias Kretzler, Robert Nelson, Keiichiro Ono, Dana Thomasova, Shrikant R Mulay, Trey Ideker, Vivette D'Agati, Ergin Beyret, Juan Carlos Izpisua Belmonte, Hans Joachim Anders, Kumar Sharma
To derive new insights in diabetic complications, we integrated publicly available human protein-protein interaction (PPI) networks with global metabolic networks using metabolomic data from patients with diabetic nephropathy. We focused on the participating proteins in the network that were computationally predicted to connect the urine metabolites. MDM2 had the highest significant number of PPI connections. As validation, significant downregulation of MDM2 gene expression was found in both glomerular and tubulointerstitial compartments of kidney biopsy tissue from 2 independent cohorts of patients with diabetic nephropathy...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27762052/generation-of-human-organs-in-pigs-via-interspecies-blastocyst-complementation
#9
J Wu, A Platero Luengo, M A Gil, K Suzuki, C Cuello, M Morales Valencia, I Parrilla, C A Martinez, A Nohalez, J Roca, E A Martinez, J C Izpisua Belmonte
More than eighteen years have passed since the first derivation of human embryonic stem cells (ESCs), but their clinical use is still met with several challenges, such as ethical concerns regarding the need of human embryos, tissue rejection after transplantation and tumour formation. The generation of human induced pluripotent stem cells (iPSCs) enables the access to patient-derived pluripotent stem cells (PSCs) and opens the door for personalized medicine as tissues/organs can potentially be generated from the same genetic background as the patient recipients, thus avoiding immune rejections or complication of immunosuppression strategies...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27610564/cellular-metabolism-and-induced-pluripotency
#10
REVIEW
Jun Wu, Alejandro Ocampo, Juan Carlos Izpisua Belmonte
The discovery of induced pluripotent stem cells (iPSCs) a decade ago, which we are celebrating in this issue of Cell, represents a landmark discovery in biomedical research. Together with somatic cell nuclear transfer, iPSC generation reveals the remarkable plasticity associated with differentiated cells and provides an unprecedented means for modeling diseases using patient samples. In addition to transcriptional and epigenetic remodeling, cellular reprogramming to pluripotency is also accompanied by a rewiring of metabolic pathways, which ultimately leads to changes in cell identities...
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27570066/3d-culture-supports-long-term-expansion-of-mouse-and-human-nephrogenic-progenitors
#11
Zhongwei Li, Toshikazu Araoka, Jun Wu, Hsin-Kai Liao, Mo Li, Marta Lazo, Bing Zhou, Yinghui Sui, Min-Zu Wu, Isao Tamura, Yun Xia, Ergin Beyret, Taiji Matsusaka, Ira Pastan, Concepcion Rodriguez Esteban, Isabel Guillen, Pedro Guillen, Josep M Campistol, Juan Carlos Izpisua Belmonte
Transit-amplifying nephron progenitor cells (NPCs) generate all of the nephrons of the mammalian kidney during development. Their limited numbers, poor in vitro expansion, and difficult accessibility in humans have slowed basic and translational research into renal development and diseases. Here, we show that with appropriate 3D culture conditions, it is possible to support long-term expansion of primary mouse and human fetal NPCs as well as NPCs derived from human induced pluripotent stem cells (iPSCs). Expanded NPCs maintain genomic stability, molecular homogeneity, and nephrogenic potential in vitro, ex vivo, and in vivo...
October 6, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27490631/looking-to-the-future-following-10-years-of-induced-pluripotent-stem-cell-technologies
#12
Mo Li, Juan Carlos Izpisua Belmonte
The development of induced pluripotent stem cells (iPSCs) has fundamentally changed our view on developmental cell-fate determination and led to a cascade of technological innovations in regenerative medicine. Here we provide an overview of the progress in the field over the past decade, as well as our perspective on future directions and clinical implications of iPSC technology.
September 2016: Nature Protocols
https://www.readbyqxmd.com/read/27426043/anti-aging-strategies-based-on-cellular-reprogramming
#13
REVIEW
Alejandro Ocampo, Pradeep Reddy, Juan Carlos Izpisua Belmonte
Aging can be defined as the progressive decline in the ability of a cell or organism to resist stress and disease. Recent advances in cellular reprogramming technologies have enabled detailed analyses of the aging process, often involving cell types derived from aged individuals, or patients with premature aging syndromes. In this review we discuss how cellular reprogramming allows the recapitulation of aging in a dish, describing novel experimental approaches to investigate the aging process. Finally, we explore the role of epigenetic dysregulation as a driver of aging, discussing how epigenetic reprogramming may be harnessed to ameliorate aging hallmarks, both in vitro and in vivo...
August 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27315475/stem-cells-a-renaissance-in-human-biology-research
#14
REVIEW
Jun Wu, Juan Carlos Izpisua Belmonte
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...
June 16, 2016: Cell
https://www.readbyqxmd.com/read/27314153/reprogramming-strategies-for-the-establishment-of-novel-human-cancer-models
#15
Ignacio Sancho-Martinez, Juan Carlos Izpisua Belmonte
Cancer comprises heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. The emergence of the "cancer stem cell" (CSC) hypothesis that they are the cells responsible for resistance, metastasis and secondary tumor appearance identifies these populations as novel obligatory targets for the treatment of cancer. CSCs, like their normal tissue-specific stem cell counterparts, are multipotent, partially differentiated, self-sustaining, yet transformed cells...
September 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27300161/characterization-of-the-epigenetic-changes-during-human-gonadal-primordial-germ-cells-reprogramming
#16
C Eguizabal, L Herrera, L De Oñate, N Montserrat, P Hajkova, J C Izpisua Belmonte
Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans...
September 2016: Stem Cells
https://www.readbyqxmd.com/read/27190034/an-overview-of-mammalian-pluripotency
#17
REVIEW
Jun Wu, Takayoshi Yamauchi, Juan Carlos Izpisua Belmonte
Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions...
May 15, 2016: Development
https://www.readbyqxmd.com/read/27179434/myocardial-commitment-from-human-pluripotent-stem-cells-rapid-production-of-human-heart-grafts
#18
Elena Garreta, Lorena de Oñate, M Eugenia Fernández-Santos, Roger Oria, Carolina Tarantino, Andreu M Climent, Andrés Marco, Mireia Samitier, Elena Martínez, Maria Valls-Margarit, Rafael Matesanz, Doris A Taylor, Francisco Fernández-Avilés, Juan Carlos Izpisua Belmonte, Nuria Montserrat
Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering...
April 26, 2016: Biomaterials
https://www.readbyqxmd.com/read/27025988/loss-of-max-results-in-meiotic-entry-in-mouse-embryonic-and-germline-stem-cells
#19
Ayumu Suzuki, Masataka Hirasaki, Tomoaki Hishida, Jun Wu, Daiji Okamura, Atsushi Ueda, Masazumi Nishimoto, Yutaka Nakachi, Yosuke Mizuno, Yasushi Okazaki, Yasuhisa Matsui, Juan Carlos Izpisua Belmonte, Akihiko Okuda
Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division...
2016: Nature Communications
https://www.readbyqxmd.com/read/27015301/the-molecular-harbingers-of-early-mammalian-embryo-patterning
#20
COMMENT
Jun Wu, Juan Carlos Izpisua Belmonte
Random or not, the mechanisms at play during the first cell-fate determination in mammalian embryos have been debated for years. Studies by Goolam et al. and White et al. shed new light on the molecular mechanisms underlying the intrinsic biases that lead to non-random lineage segregation in early mammalian development.
March 24, 2016: Cell
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