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stem cell heterogeneity

Nickesha C Anderson, Meghan A Van Zandt, Swechhya Shrestha, Daniel B Lawrence, Jyoti Gupta, Christopher Y Chen, Felicia A Harrsch, Trinithas Boyi, Carolyn E Dundes, Gloster Aaron, Janice R Naegele, Laura Grabel
GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns...
October 5, 2018: Stem Cell Research
Zhennan Tao, Tao Li, Haiwen Ma, Yihan Yang, Chen Zhang, Long Hai, Peidong Liu, Feng Yuan, Jiabo Li, Li Yi, Luqing Tong, Yingshuai Wang, Yang Xie, Haolang Ming, Shengping Yu, Xuejun Yang
Autophagy is a vital process that involves degradation of long-lived proteins and dysfunctional organelles and contributes to cellular metabolism. Glioma-initiating cells (GICs) have the ability to self-renew, differentiate into heterogeneous types of tumor cells, and sustain tumorigenicity; thus, GICs lead to tumor recurrence. Accumulating evidence indicates that autophagy can induce stem cell differentiation and increase the lethality of temozolomide against GICs. However, the mechanism underlying the regulation of GIC self-renewal by autophagy remains uncharacterized...
October 18, 2018: Cell Death & Disease
Neha Sharma, Lisamarie Moore, Shravanthi Chidambaram, Nicholas W Colangelo, Sonia M de Toledo, Edouard I Azzam
Neural stem cells are attracting enormous attention in regenerative medicine due to their ability to self-renew and differentiate into the cell lineages that constitute the central nervous system. However, little is known about the mechanism underlying the regulation of their redox environment, which is essential for homeostatic cellular functions. The redox-modulated c-Jun N-terminal kinases (JNK) are a molecular switch in stress signal transduction and are involved in numerous brain functions. Using a selective but broad-spectrum inhibitor of JNK 1/2/3, we investigated the role of JNK in regulating the levels of reactive oxygen species in mitochondria, mitochondrial membrane potential, viability, proliferation and lineage alterations in human H9-derived neural stem/progenitor cells (NSPs)...
October 18, 2018: Developmental Neuroscience
Song Xu, Sanggu Kim, Irvin S Y Chen, Tom Chou
In a recent clone-tracking experiment, millions of uniquely tagged hematopoietic stem cells (HSCs) were autologously transplanted into rhesus macaques and peripheral blood containing thousands of tags were sampled and sequenced over 14 years to quantify the abundance of hundreds to thousands of tags or "clones." Two major puzzles of the data have been observed: consistent differences and massive temporal fluctuations of clone populations. The large sample-to-sample variability can lead clones to occasionally go "extinct" but "resurrect" themselves in subsequent samples...
October 18, 2018: PLoS Computational Biology
Leonard Y M Cheung, Akima S George, Stacey R McGee, Alexandre Z Daly, Michelle L Brinkmeier, Buffy S Ellsworth, Sally A Camper
Transcription factors and signaling pathways that regulate stem cells and specialized hormone-producing cells in the pituitary gland have been the subject of intense study and have yielded a mechanistic understanding of pituitary organogenesis and disease. Yet, the regulation of stem cell proliferation and differentiation, the heterogeneity among specialized hormone-producing cells, and the role of non-endocrine cells in the gland remain important, unanswered questions. Recent advances in single-cell RNA sequencing (scRNAseq) technologies provide new avenues to address these questions...
October 17, 2018: Endocrinology
Olatoyosi Odenike
The classic Philadelphia chromosome negative myeloproliferative neoplasms (Ph -MPNs) are a heterogeneous group of hematopoietic stem cell diseases, characterized by activated JAK/STAT signaling, significant phenotypic mimicry, including a propensity for evolution to myeloid blast phase disease. Effective therapeutic options are limited for patients with Ph-MPNs in the blast phase (MPN-BP), and allogeneic stem cell transplant is the only known cure. Our increasing understanding of the molecular pathogenesis of this group of diseases, coupled with the increasing availability of targeted agents, has the potential to inform new subset specific therapeutic approaches...
October 17, 2018: Blood
Zhiqing Li, Shuxun Liu, Junfang Xu, Xiang Zhang, Dan Han, Juan Liu, Meng Xia, Lin Yi, Qicong Shen, Sheng Xu, Linrong Lu, Xuetao Cao
Tissue-resident mast cells are associated with many inflammatory and physiological processes. Although mast cells arise from the yolk sac, the exact ontogeny of adult mast cells remains unclear. Here we have investigated the hematopoietic origin of mast cells using fate-mapping systems. We have shown that early erythro-myeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells (HSCs) each gave rise to mast cells in succession via an intermediate integrin β7+ progenitor. From late embryogenesis to adult, early EMP-derived mast cells were largely replaced by late EMP-derived cells in most connective tissues except adipose and pleural cavity...
October 16, 2018: Immunity
Huating Yuan, Min Yan, Guanxiong Zhang, Wei Liu, Chunyu Deng, Gaoming Liao, Liwen Xu, Tao Luo, Haoteng Yan, Zhilin Long, Aiai Shi, Tingting Zhao, Yun Xiao, Xia Li
High functional heterogeneity of cancer cells poses a major challenge for cancer research. Single-cell sequencing technology provides an unprecedented opportunity to decipher diverse functional states of cancer cells at single-cell resolution, and cancer scRNA-seq datasets have been largely accumulated. This emphasizes the urgent need to build a dedicated resource to decode the functional states of cancer single cells. Here, we developed CancerSEA ( or, the first dedicated database that aims to comprehensively explore distinct functional states of cancer cells at the single-cell level...
October 17, 2018: Nucleic Acids Research
Amar Desai, Yan Yan, Stanton L Gerson
Cancer stem cells (CSCs) are a subpopulation of cells within tumors that possess the stem cell characteristics of self-renewal, quiescence, differentiation, and the ability to recapitulate the parental tumor when transplanted into a host. CSCs are correlated with poor clinical outcome due to their contribution to chemotherapy resistance and metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs within a heterogeneous tumor, and here we summarize ongoing preclinical and clinical efforts to therapeutically target these cells and improve patient outcomes...
October 17, 2018: Stem Cells Translational Medicine
Paola Caria, Tinuccia Dettori, Daniela Virginia Frau, Daniel Lichtenzstejn, Fabiana Pani, Roberta Vanni, Sabine Mai
The relationship between the three-dimensional (3D) nuclear telomere architecture and specific genetic alterations in papillary thyroid carcinoma (PTC), in particular in cancer stem-like cells (CSLCs), has not yet been investigated. We isolated thyrospheres containing CSLCs from B-CPAP, K1, and TPC-1 PTC-derived cell lines, representative of tumors with different genetic backgrounds within the newly identified BRAFV600E -like PTC subgroup, and used immortalized normal human thyrocytes (Nthy-ori 3.1) as control...
October 17, 2018: Journal of Cellular Physiology
Bruna Codispoti, Massimo Marrelli, Francesco Paduano, Marco Tatullo
Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues-technical issues as well as regulatory and ethical concerns-thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150⁻1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types...
October 15, 2018: Journal of Clinical Medicine
Ludivine Coudière Morrison, Nazanin Tatari, Tamra E Werbowetski-Ogilvie
Utilization of human embryonic stem cells (hESCs) as a model system to study highly malignant pediatric cancers has led to significant insight into the molecular mechanisms governing tumor progression and has revealed novel therapeutic targets for these devastating diseases. Here, we describe a method for generating heterogeneous populations of neural precursors from both normal and neoplastic hESCs and the subsequent injection of neoplastic human embryonic neural cells (hENs) into intracerebellar or intracranial xenograft models...
2019: Methods in Molecular Biology
Mathieu Seyfrid, David Bobrowski, David Bakhshinyan, Nazanin Tatari, Chitra Venugopal, Sheila K Singh
Early development of human organisms relies on stem cells, a population of non-specialized cells that can divide symmetrically to give rise to two identical daughter cells, or divide asymmetrically to produce one identical daughter cell and another more specialized cell. The capacity to undergo cellular divisions while maintaining an undifferentiated state is termed self-renewal and is responsible for the maintenance of stem cell populations during development. In addition, self-renewal plays a crucial role in the homeostasis of developed organism through replacement of defective cells...
2019: Methods in Molecular Biology
Nicolas Yelle, David Bakhshinyan, Chitra Venugopal, Sheila K Singh
From stem cells, to the cancer stem cell hypothesis and intratumoral heterogeneity, the following introductory chapter on brain tumor stem cells explores the history of normal and cancerous stem cells, and their implication in the current model of brain tumor development. The origins of stem cells date back to the 1960s, when they were first described as cells capable of self-renewal, extensive proliferation, and differentiation. Since then, many advances have been made and adult stem cells are now known to be present in a very wide variety of tissues...
2019: Methods in Molecular Biology
Mubeen Khan, Zeinab Fadaie, Stéphanie S Cornelis, Frans P M Cremers, Susanne Roosing
Inherited retinal diseases (IRDs) display a very high degree of clinical and genetic heterogeneity, which poses challenges in finding the underlying defects in known IRD-associated genes and in identifying novel IRD-associated genes. Knowledge on the molecular and clinical aspects of IRDs has increased tremendously in the last decade. Here, we outline the state-of-the-art techniques to find the causative genetic variants, with special attention for next-generation sequencing which can combine molecular diagnostics and retinal disease gene identification...
2019: Methods in Molecular Biology
Kelly Ceyzériat, Lucile Ben Haim, Audrey Denizot, Dylan Pommier, Marco Matos, Océane Guillemaud, Marie-Ange Palomares, Laurene Abjean, Fanny Petit, Pauline Gipchtein, Marie-Claude Gaillard, Martine Guillermier, Sueva Bernier, Mylène Gaudin, Gwenaëlle Aurégan, Charlène Joséphine, Nathalie Déchamps, Julien Veran, Valentin Langlais, Karine Cambon, Alexis P Bemelmans, Jan Baijer, Gilles Bonvento, Marc Dhenain, Jean-François Deleuze, Stéphane H R Oliet, Emmanuel Brouillet, Philippe Hantraye, Maria-Angeles Carrillo-de Sauvage, Robert Olaso, Aude Panatier, Carole Escartin
Astrocyte reactivity and neuroinflammation are hallmarks of CNS pathological conditions such as Alzheimer's disease. However, the specific role of reactive astrocytes is still debated. This controversy may stem from the fact that most strategies used to modulate astrocyte reactivity and explore its contribution to disease outcomes have only limited specificity. Moreover, reactive astrocytes are now emerging as heterogeneous cells and all types of astrocyte reactivity may not be controlled efficiently by such strategies...
October 16, 2018: Acta Neuropathologica Communications
Courtney M Schaal, Namrata Bora-Singhal, Durairaj Mohan Kumar, Srikumar P Chellappan
BACKGROUND: Lung cancer is the leading cause of cancer related deaths and its incidence is highly correlated with cigarette smoking. Nicotine, the addictive component of tobacco smoke, cannot initiate tumors, but can promote proliferation, migration, and invasion of cells in vitro and promote tumor growth and metastasis in vivo. This nicotine-mediated tumor promotion is facilitated through the activation of nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers...
October 15, 2018: Molecular Cancer
Claudia Matteucci, Emanuela Balestrieri, Ayele Argaw-Denboba, Paola Sinibaldi-Vallebona
Cancer incidence and mortality, metastasis, drug resistance and recurrence are still the critical issues of oncological diseases. In this scenario, increasing scientific evidences demonstrate that the activation of human endogenous retroviruses (HERVs) is involved in the aggressiveness of tumors such as melanoma, breast, germ cell, renal, ovarian, liver and haematological cancers. In their dynamic regulation, HERVs have also proved to be important determinants of pluripotency in human embryonic stem cells (ESC) and of the reprogramming process of induced pluripotent stem cells (iPSCs)...
October 11, 2018: Seminars in Cancer Biology
Jean-Stéphane Joly, Vincent Tropepe
No abstract text is available yet for this article.
November 2018: Progress in Neurobiology
Amer M Zeidan, Rory M Shallis, Rong Wang, Amy Davidoff, Xiaomei Ma
Myelodysplastic syndromes (MDS) consist of a heterogeneous group of myeloid neoplasms characterized by inefficient hematopoiesis, variable cytopenias and a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS has been hampered by evolving diagnostic criteria and delayed classification of MDS as cancers until 2001. The poorly-understood nature of these neoplasms combined with the lack of effective therapies for decades contributed to suboptimal case ascertainment and underreporting...
September 21, 2018: Blood Reviews
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