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Cell Stem Cell

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https://www.readbyqxmd.com/read/28526555/modeling-psychomotor-retardation-using-ipscs-from-mct8-deficient-patients-indicates-a-prominent-role-for-the-blood-brain-barrier
#1
Gad D Vatine, Abraham Al-Ahmad, Bianca K Barriga, Soshana Svendsen, Ariel Salim, Leslie Garcia, Veronica J Garcia, Ritchie Ho, Nur Yucer, Tongcheng Qian, Ryan G Lim, Jie Wu, Leslie M Thompson, Weston R Spivia, Zhaohui Chen, Jennifer Van Eyk, Sean P Palecek, Samuel Refetoff, Eric V Shusta, Clive N Svendsen
Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype...
May 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28506464/recruited-monocytes-and-type-2-immunity-promote-lung-regeneration-following-pneumonectomy
#2
Andrew J Lechner, Ian H Driver, Jinwoo Lee, Carmen M Conroy, Abigail Nagle, Richard M Locksley, Jason R Rock
To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes...
May 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28506465/deconstructing-olfactory-stem-cell-trajectories-at-single-cell-resolution
#3
Russell B Fletcher, Diya Das, Levi Gadye, Kelly N Street, Ariane Baudhuin, Allon Wagner, Michael B Cole, Quetzal Flores, Yoon Gi Choi, Nir Yosef, Elizabeth Purdom, Sandrine Dudoit, Davide Risso, John Ngai
A detailed understanding of the paths that stem cells traverse to generate mature progeny is vital for elucidating the mechanisms governing cell fate decisions and tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell lineages in the olfactory epithelium. Here we integrate single-cell RNA sequencing and robust statistical analyses with in vivo lineage tracing to define a detailed map of the postnatal olfactory epithelium, revealing cell fate potentials and branchpoints in olfactory stem cell lineage trajectories...
April 28, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28457749/an-fak-yap-mtor-signaling-axis-regulates-stem-cell-based-tissue-renewal-in-mice
#4
Jimmy Kuang-Hsien Hu, Wei Du, Samuel J Shelton, Michael C Oldham, C Michael DiPersio, Ophir D Klein
Tissue homeostasis requires the production of newly differentiated cells from resident adult stem cells. Central to this process is the expansion of undifferentiated intermediates known as transit-amplifying (TA) cells, but how stem cells are triggered to enter this proliferative TA state remains an important open question. Using the continuously growing mouse incisor as a model of stem cell-based tissue renewal, we found that the transcriptional cofactors YAP and TAZ are required both to maintain TA cell proliferation and to inhibit differentiation...
April 18, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28457750/single-cell-rna-seq-analysis-maps-development-of-human-germline-cells-and-gonadal-niche-interactions
#5
Li Li, Ji Dong, Liying Yan, Jun Yong, Xixi Liu, Yuqiong Hu, Xiaoying Fan, Xinglong Wu, Hongshan Guo, Xiaoye Wang, Xiaohui Zhu, Rong Li, Jie Yan, Yuan Wei, Yangyu Zhao, Wei Wang, Yixin Ren, Peng Yuan, Zhiqiang Yan, Boqiang Hu, Fan Guo, Lu Wen, Fuchou Tang, Jie Qiao
Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here we performed single-cell RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and male human embryos spanning several developmental stages. We found that female FGCs undergo four distinct sequential phases characterized by mitosis, retinoic acid signaling, meiotic prophase, and oogenesis...
April 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28457748/gli1-mesenchymal-stromal-cells-are-a-key-driver-of-bone-marrow-fibrosis-and-an-important-cellular-therapeutic-target
#6
Rebekka K Schneider, Ann Mullally, Aurelien Dugourd, Fabian Peisker, Remco Hoogenboezem, Paulina M H Van Strien, Eric M Bindels, Dirk Heckl, Guntram Büsche, David Fleck, Gerhard Müller-Newen, Janewit Wongboonsin, Monica Ventura Ferreira, Victor G Puelles, Julio Saez-Rodriguez, Benjamin L Ebert, Benjamin D Humphreys, Rafael Kramann
Bone marrow fibrosis (BMF) develops in various hematological and non-hematological conditions and is a central pathological feature of myelofibrosis. Effective cell-targeted therapeutics are needed, but the cellular origin of BMF remains elusive. Here, we show using genetic fate tracing in two murine models of BMF that Gli1(+) mesenchymal stromal cells (MSCs) are recruited from the endosteal and perivascular niche to become fibrosis-driving myofibroblasts in the bone marrow. Genetic ablation of Gli1(+) cells abolished BMF and rescued bone marrow failure...
April 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28366589/h3k4-methylation-dependent-memory-of-somatic-cell-identity-inhibits-reprogramming-and-development-of-nuclear-transfer-embryos
#7
Eva Hörmanseder, Angela Simeone, George E Allen, Charles R Bradshaw, Magdalena Figlmüller, John Gurdon, Jerome Jullien
Vertebrate eggs can induce the nuclear reprogramming of somatic cells to enable production of cloned animals. Nuclear reprogramming is relatively inefficient, and the development of the resultant embryos is frequently compromised, in part due to the inappropriate expression of genes previously active in the donor nucleus. Here, we identify H3K4 methylation as a major epigenetic roadblock that limits transcriptional reprogramming and efficient nuclear transfer (NT). Widespread expression of donor-cell-specific genes was observed in inappropriate cell types in NT embryos, limiting their developmental capacity...
March 23, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28366587/efficient-derivation-of-functional-human-airway-epithelium-from-pluripotent-stem-cells-via-temporal-regulation-of-wnt-signaling
#8
Katherine B McCauley, Finn Hawkins, Maria Serra, Dylan C Thomas, Anjali Jacob, Darrell N Kotton
Effective derivation of functional airway organoids from induced pluripotent stem cells (iPSCs) would provide valuable models of lung disease and facilitate precision therapies for airway disorders such as cystic fibrosis. However, limited understanding of human airway patterning has made this goal challenging. Here, we show that cyclical modulation of the canonical Wnt signaling pathway enables rapid directed differentiation of human iPSCs via an NKX2-1(+) progenitor intermediate into functional proximal airway organoids...
March 22, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28343983/comprehensive-cell-surface-protein-profiling-identifies-specific-markers-of-human-naive-and-primed-pluripotent-states
#9
Amanda J Collier, Sarita P Panula, John Paul Schell, Peter Chovanec, Alvaro Plaza Reyes, Sophie Petropoulos, Anne E Corcoran, Rachael Walker, Iyadh Douagi, Fredrik Lanner, Peter J Rugg-Gunn
Human pluripotent stem cells (PSCs) exist in naive and primed states and provide important models to investigate the earliest stages of human development. Naive cells can be obtained through primed-to-naive resetting, but there are no reliable methods to prospectively isolate unmodified naive cells during this process. Here we report comprehensive profiling of cell surface proteins by flow cytometry in naive and primed human PSCs. Several naive-specific, but not primed-specific, proteins were also expressed by pluripotent cells in the human preimplantation embryo...
March 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28330582/adipocyte-accumulation-in-the-bone-marrow-during-obesity-and-aging-impairs-stem-cell-based-hematopoietic-and-bone-regeneration
#10
Thomas H Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W Logan, Annette Schürmann, Luis R Saraiva, Tim J Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation...
March 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28285904/mex3a-marks-a-slowly-dividing-subpopulation-of-lgr5-intestinal-stem-cells
#11
Francisco M Barriga, Elisa Montagni, Miyeko Mana, Maria Mendez-Lago, Xavier Hernando-Momblona, Marta Sevillano, Amy Guillaumet-Adkins, Gustavo Rodriguez-Esteban, Simon J A Buczacki, Marta Gut, Holger Heyn, Douglas J Winton, Omer H Yilmaz, Camille Stephan-Otto Attolini, Ivo Gut, Eduard Batlle
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes...
March 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475885/proteostatic-and-metabolic-control-of-stemness
#12
REVIEW
Laura García-Prat, Pedro Sousa-Victor, Pura Muñoz-Cánoves
Adult stem cells, particularly those resident in tissues with little turnover, are largely quiescent and only activate in response to regenerative demands, while embryonic stem cells continuously replicate, suggesting profoundly different regulatory mechanisms within distinct stem cell types. In recent years, evidence linking metabolism, mitochondrial dynamics, and protein homeostasis (proteostasis) as fundamental regulators of stem cell function has emerged. Here, we discuss new insights into how these networks control potency, self-renewal, differentiation, and aging of highly proliferative embryonic stem cells and quiescent adult stem cells, with a focus on hematopoietic and muscle stem cells and implications for anti-aging research...
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475884/hematopoiesis-reconciling-historic-controversies-about-the-niche
#13
Ninib Baryawno, Nicolas Severe, David T Scadden
The niche, as first conceptualized, was in conflict with the prevailing wisdom that stem cells have internal logic. The niche hypothesis has been indisputably confirmed. Yet, recent findings indicate little plasticity of epigenetically scripted hematopoietic stem/progenitors. Reconciling this conflict requires re-envisioning the niche as an enabler, not designer, of cell fate.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475883/are-perivascular-adipocyte-progenitors-mural-cells-or-adventitial-fibroblasts
#14
LETTER
Nuno Guimarães-Camboa, Sylvia M Evans
In their reply, Sylvia Evans and colleagues argue that their lineage-labeling approach gives more precise tracing of the lineage contribution of mural cells in vivo than previous versions.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475882/do-adipocytes-emerge-from-mural-progenitors
#15
LETTER
Lavanya Vishvanath, Jonathan Z Long, Bruce M Spiegelman, Rana K Gupta
Gupta and colleagues highlight recent work, including their own, that suggested based on lineage tracing that mural cells are adipogenic, contrasting with the conclusions of a recent Cell Stem Cell paper.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475881/eyeing-the-fountain-of-youth
#16
Magali Saint-Geniez, Mariana Aparecida B Rosales
Stem cell-based disease modeling is an emerging technology for the mechanistic study and therapeutic screening of complex ocular pathologies. In this issue of Cell Stem Cell, Saini et al. (2017) show that iPSC-derived RPE cells from age-related macular degeneration patients express increased levels of pro-inflammatory factors that can be normalized by the anti-aging drug nicotinamide.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475880/synthetic-embryos-windows-into-mammalian-development
#17
Aryeh Warmflash
Mammalian embryonic stem cells (ESCs) can self-organize in vitro, but whether they can recreate early embryonic morphogenesis is unclear. Harrison et al. recently demonstrate in Science that 3D co-cultures of mouse ESCs and trophoblast stem cells self-organize into embryo-like structures that recreate many features of early mouse development.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475879/gmp-ing-to-spatial-conclusions-about-emergency-and-leukemic-myelopoiesis
#18
Madeline Niederkorn, Daniel T Starczynowski
Hematopoietic stem cells (HSCs) in the bone marrow (BM) form mature blood cells of all lineages through expansion of lineage-biased progenitors. In a recent issue of Nature, Hérault et al. (2017) uncover a unique spatiotemporal mechanism of granulocyte-macrophage progenitors (GMPs) employed in emergency hematopoiesis that is also hijacked in leukemia.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475878/gotta-have-gata-for-human-pancreas-development
#19
David S Lorberbaum, Lori Sussel
Haploinsufficient GATA6 mutations are associated with human pancreatic agenesis. Shi et al. (2017) in this issue of Cell Stem Cell and Tiyaboonchai et al. (2017) in a recent issue of Cell Reports utilize hPSCs to characterize GATA6 function during human pancreas development. One functional copy of GATA6 is sufficient for definitive endoderm development and pancreas formation, but it is inadequate for functional β cell differentiation.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28475877/joining-forces-bmi1-inhibition-and-cisplatin-curb-squamous-carcinogenesis
#20
Jessie A Brown, Markus Schober
Head and neck squamous cell carcinomas (HNSCCs) are refractory to therapeutic interventions. Chen et al. (2017) show that mouse and human HNSCCs and their metastases depend on Bmi1-expressing cancer stem cells and AP1 signaling and that simultaneously inhibiting Bmi1 or AP1, combined with Cisplatin, reduces tumor growth effectively in preclinical models.
May 4, 2017: Cell Stem Cell
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