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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
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
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
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
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
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
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
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
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
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
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
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
Nuria Montserrat, Elena Garreta, Juan Carlos Izpisua Belmonte
The kidney is the most important organ for water homeostasis and waste excretion. It performs several important physiological functions for homeostasis: it filters the metabolic waste out of circulation, regulates body fluid balances, and acts as an immune regulator and modulator of cardiovascular physiology. The development of in vitro renal disease models with pluripotent stem cells (both human embryonic stem cells and induced pluripotent stem cells) and the generation of robust protocols for in vitro derivation of renal-specific-like cells from patient induced pluripotent stem cells have just emerged...
September 2016: FEBS Journal
Ignacio Sancho-Martinez, Emmanuel Nivet, Yun Xia, Tomoaki Hishida, Aitor Aguirre, Alejandro Ocampo, Li Ma, Robert Morey, Marie N Krause, Andreas Zembrzycki, Olaf Ansorge, Eric Vazquez-Ferrer, Ilir Dubova, Pradeep Reddy, David Lam, Yuriko Hishida, Min-Zu Wu, Concepcion Rodriguez Esteban, Dennis O'Leary, Geoffrey M Wahl, Inder M Verma, Louise C Laurent, Juan Carlos Izpisua Belmonte
Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis...
2016: Nature Communications
Lina Fu, Xiuling Xu, Ruotong Ren, Jun Wu, Weiqi Zhang, Jiping Yang, Xiaoqing Ren, Si Wang, Yang Zhao, Liang Sun, Yang Yu, Zhaoxia Wang, Ze Yang, Yun Yuan, Jie Qiao, Juan Carlos Izpisua Belmonte, Jing Qu, Guang-Hui Liu
Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated...
March 2016: Protein & Cell
Mo Li, Juan Carlos Izpisua Belmonte
More people die every year from ischemic heart disease than any other disease. Because the human heart lacks sufficient ability to replenish the damaged cardiac muscles, extensive research has been devoted toward understanding the homeostatic and regenerative potential of the heart and to develop regenerative therapies for heart disease. Here, we discuss recent advances in the understanding of mechanisms governing heart growth during homeostasis or injury, including those from observational studies in humans and experimental research in animal models of cardiac regeneration...
January 22, 2016: Circulation Research
Josep M Campistol
No abstract text is available yet for this article.
October 2015: Transplantation Proceedings
Jun Wu, Juan Carlos Izpisua Belmonte
The past decade's rapid progress in human pluripotent stem cell (hPSC) research has generated hope for meeting the rising demand of organ donation, which remains the only effective cure for end-stage organ failure, a major cause of death worldwide. Despite the potential, generation of transplantable organs from hPSCs using in vitro differentiation is far-fetched. An in vivo interspecies chimeric complementation strategy relying on chimeric-competent hPSCs and zygote genome editing provides an auspicious alternative for providing unlimited organ source for transplantation...
June 2016: Transgenic Research
Ergin Beyret, Juan Carlos Izpisua Belmonte
Reprogramming to pluripotency has thus far required complex procedures involving nuclear transfer, cell fusion or genetic manipulation. Two recent papers from Hongkui Deng's group now show various cell types can be reprogrammed simply by chemicals through an extraembryonic endoderm-like phase instead of the primitive streak-like mesendoderm induced by Yamanaka factors.
February 2016: Cell Research
Marie N Krause, Ignacio Sancho-Martinez, Juan Carlos Izpisua Belmonte
Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called "Pioneer TFs", play an important role during the stochastic phase of iPSC reprogramming [2-6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin...
May 6, 2016: Biochemical and Biophysical Research Communications
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