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stem cell heterogeneity

Michail E Klontzas, Supachai Reakasame, Raquel Silva, Jose C F Morais, Spyros Vernardis, Robert J MacFarlane, Manolis Heliotis, Eleftherios Tsiridis, Nicki Panoskaltsis, Aldo R Boccaccini, Athanasios Mantalaris
Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation...
February 14, 2019: Acta Biomaterialia
Michael Huber, Andrew C B Cato, George K Ainooson, Marc Freichel, Volodymyr Tsvilovskyy, Rolf Jessberger, Eva Riedlinger, Christian P Sommerhoff, Stephan C Bischoff
Mast cells, best known for their detrimental role in allergic diseases, act in a diverse array of physiological and pathological functions, made possible by the plurality of mast cell types. Their various developmental avenues and their distinct sensitivity to (micro-) environmental conditions convey extensive heterogeneity, resulting in diverse functions. We briefly summarize this heterogeneity, elaborate on molecular determinants that allow mast cells to communicate with their environment to fulfill their tasks, discuss their protease repertoire stored in secretory lysosomes, and consider different aspects of mast cell signaling...
February 14, 2019: Journal of Allergy and Clinical Immunology
Lin Guo, Lihui Lin, Xiaoshan Wang, Mingwei Gao, Shangtao Cao, Yuanbang Mai, Fang Wu, Junqi Kuang, He Liu, Jiaqi Yang, Shilong Chu, Hong Song, Dongwei Li, Yujian Liu, Kaixin Wu, Jiadong Liu, Jinyong Wang, Guangjin Pan, Andrew P Hutchins, Jing Liu, Duanqing Pei, Jiekai Chen
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR). We further show that Klf4 contributes to Cd34+/Fxyd5+/Psca+ keratinocyte-like NR fate and that IFN-γ impedes the final transition to chimera-competent pluripotency along the RP cells...
February 13, 2019: Molecular Cell
Depeng Fang, Pan Jin, Quanxin Huang, Yuan Yang, Jinmin Zhao, Li Zheng
The tissue engineering technique using mesenchymal stem cells (MSCs) and scaffolds is promising. Transforming growth factor-β1 (TGF-β1) is generally accepted as an chondrogenic agent, but immunorejection and unexpected side effects, such as tumorigenesis and heterogeneity, limit its clinical application. Autogenous platelet-rich plasma (PRP), marked by low immunogenicity, easy accessibility, and low-cost, may be favorable for cartilage regeneration. In our study, the effect of PRP on engineered cartilage constructed by MSCs and collagen hydrogel in vitro and in vivo was investigated and compared with TGF-β1...
February 15, 2019: Journal of Cellular Physiology
Alessandro Bertolo, Martin Baur, Julien Guerrero, Tobias Pötzel, Jivko Stoyanov
Mesenchymal stromal cells (MSC) are used in cell therapies, however cellular senescence increases heterogeneity of cell populations and leads to uncertainty in therapies' outcomes. The determination of cellular senescence is time consuming and logistically intensive. Here, we propose the use of endogenous autofluorescence as real-time quantification of cellular senescence in human MSC, based on label-free flow cytometry analysis. We correlated cell autofluorescence to senescence using senescence-associated beta-galactosidase assay (SA-β-Gal) with chromogenic (X-GAL) and fluorescent (C12 FDG) substrates, gene expression of senescence markers (such as p16INK4A , p18INK4C , CCND2 and CDCA7) and telomere length...
February 14, 2019: Scientific Reports
Alba Rodriguez-Meira, Gemma Buck, Sally-Ann Clark, Benjamin J Povinelli, Veronica Alcolea, Eleni Louka, Simon McGowan, Angela Hamblin, Nikolaos Sousos, Nikolaos Barkas, Alice Giustacchini, Bethan Psaila, Sten Eirik W Jacobsen, Supat Thongjuea, Adam J Mead
Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving transcriptional heterogeneity. However, its application to studying cancerous tissues is currently hampered by the lack of coverage across key mutation hotspots in the vast majority of cells; this lack of coverage prevents the correlation of genetic and transcriptional readouts from the same single cell. To overcome this, we developed TARGET-seq, a method for the high-sensitivity detection of multiple mutations within single cells from both genomic and coding DNA, in parallel with unbiased whole-transcriptome analysis...
February 11, 2019: Molecular Cell
Catharina Melzer, Juliane von der Ohe, Ralf Hass
Cellular communication within the tumor microenvironment enables important interactions between cancer cells and recruited adjacent populations including mesenchymal stroma/stem-like cells (MSC). These interactions were monitored in vivo following co-injection of GFP-labeled human MSC together with mcherry-labeled MDA-MB-231 breast cancer cells in NODscid mice. Within 14 days of tumor development the number of initially co-injected MSC had significantly declined and spontaneous formation of breast cancer/MSC hybrid cells was observed by the appearance of double fluorescing cells...
February 5, 2019: Cancers
Fernando Vieira Pericole, Mariana Lazarini, Luciana Bueno de Paiva, Adriana da Silva Santos Duarte, Karla Priscila Vieira Ferro, Fernanda Soares Niemann, Fernanda Marconi Roversi, Sara Teresinha Olalla Saad
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell-based disorders characterized by ineffective hematopoiesis, increased genomic instability and a tendency to progress toward acute myeloid leukemia (AML). MDS and AML cells present genetic and epigenetic abnormalities and, due to the heterogeneity of these molecular alterations, the current treatment options remain unsatisfactory. Hypomethylating agents (HMA), especially azacitidine, are the mainstay of treatment for high-risk MDS patients and HMA are used in treating elderly AML...
2019: Frontiers in Oncology
Irit Meivar-Levy, Fatima Zoabi, Gil Nardini, Eugenia Manevitz-Mendelson, Gil S Leichner, Oranit Zadok, Michael Gurevich, Eytan Mor, Simona Dima, Irinel Popescu, Aviv Barzilai, Sarah Ferber, Shoshana Greenberger
BACKGROUND: Insulin-dependent diabetes is a multifactorial disorder that could be theoretically cured by functional pancreatic islets and insulin-producing cell (IPC) implantation. Regenerative medicine approaches include the potential for growing tissues and organs in the laboratory and transplanting them when the body cannot heal itself. However, several obstacles remain to be overcome in order to bring regenerative medicine approach for diabetes closer to its clinical implementation; the cells generated in vitro are typically of heterogenic and immature nature and the site of implantation should be readily vascularized for the implanted cells to survive in vivo...
February 13, 2019: Stem Cell Research & Therapy
Beomseok Kim, Eunmin Lee, Jong Kyoung Kim
Profiling the transcriptomes of individual cells with single-cell RNA sequencing (scRNA-seq) has been widely applied to provide a detailed molecular characterization of cellular heterogeneity within a population of cells. Despite recent technological advances of scRNA-seq, technical variability of gene expression in scRNA-seq is still much higher than that in bulk RNA-seq. Accounting for technical variability is therefore a prerequisite for correctly analyzing single-cell data. This chapter describes a computational pipeline for detecting highly variable genes exhibiting higher cell-to-cell variability than expected by technical noise...
2019: Methods in Molecular Biology
Patricia Dauer, Nikita S Sharma, Vineet K Gupta, Brittany Durden, Roey Hadad, Santanu Banerjee, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory protein 78 (GRP78), the master regulator of the UPR, plays a role in proliferation, invasion, and metastasis in cancer. Cancer stem cells (CSCs) make up a crucial component of the tumor heterogeneity in pancreatic cancer, as well as other cancers. "Stemness" in pancreatic cancer defines a population of cells within the tumor that have increased therapeutic resistance as well as survival advantage...
February 12, 2019: Cell Death & Disease
Jacek Pietrzak, Marek Mirowski, Agnieszka Jeleń, Rafał Świechowski, Damian Wodziński, Katarzyna Niebudek, Ewa Balcerczak
Acute myeloid leukaemia (AML) is a heterogeneous disorder of haematopoietic stem cells or progenitor cells. Metalloproteinases (MMPs) are proteolytic enzymes whose activity is increased in different types of solid tumours. These enzymes regulate many processes associated with tumour progression. In haematological malignancy, the role of MMPs seems to be underestimated, and only metalloproteinase 2 (MMP2) and metalloproteinase 9 (MMP9) have been widely examined so far. In this work, differences in metalloproteinase 1 (MMP1) gene expression between patients with AML and healthy individuals were assessed...
February 12, 2019: Molecular Biology Reports
Eric Deneault, Muhammad Faheem, Sean H White, Deivid C Rodrigues, Song Sun, Wei Wei, Alina Piekna, Tadeo Thompson, Jennifer L Howe, Leon Chalil, Vickie Kwan, Susan Walker, Peter Pasceri, Frederick P Roth, Ryan Kc Yuen, Karun K Singh, James Ellis, Stephen W Scherer
Induced pluripotent stem cell (iPSC)-derived neurons are increasingly used to model Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of penetrant and weaker polygenic risk variants to ASD, 'isogenic' iPSC-derived neurons are critical. We developed a set of procedures to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD...
February 12, 2019: ELife
Amita Ajit, Santhoshkumar Thankayyan Retnabai, Lissy K Krishnan
Biotechnological interventions to engineer favorable biochemical environments that facilitate wound repair through quick attainment of vasculature are of immense demand. Potential of angiogenic factors (AF), notably vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (Hif-1α) and the paracrine role of human adipose derived mesenchymal stromal cells (hADMSCs) in establishing vasculature has been reported. Independent application of AF or hADMSCs has led to clinical failure, pertaining to poor means of delivery, deprived bioavailability and insufficiency to drive adequate angiogenesis, respectively...
February 12, 2019: Tissue Engineering. Part C, Methods
Xiaoshi Jia, Richard J Miron, Chengcheng Yin, Hudi Xu, Tao Luo, Jiwei Wang, Rong Jia, Min Wu, Yufeng Zhang, Yuhong Li
Osteoporosis has been shown to intensify bone loss caused by periodontitis and both share common risk factors. One strategy utilized to manage the disease has been via the release of Sr ions by Strontium Ranelate having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously we have developed and characterized porous Sr-mesoporous bioactive glass (Sr-MBG) scaffolds and demonstrated their ability to promote periodontal regeneration when compared to MBG alone. Our group further discovered a splicing factor, heterogeneous nuclear ribonucleoprotein L (hnRNPL), was drastically down-regulated in periodontal ligament stem cells (PDLCs) stimulated by Sr through the activation of AKT pathway...
February 12, 2019: Journal of Cellular and Molecular Medicine
Sandra Pinho, Paul S Frenette
The haematopoietic stem cell (HSC) microenvironment in the bone marrow, termed the niche, ensures haematopoietic homeostasis by controlling the proliferation, self-renewal, differentiation and migration of HSCs and progenitor cells at steady state and in response to emergencies and injury. Improved methods for HSC isolation, driven by advances in single-cell and molecular technologies, have led to a better understanding of their behaviour, heterogeneity and lineage fate and of the niche cells and signals that regulate their function...
February 11, 2019: Nature Reviews. Molecular Cell Biology
Kenji Kawabe, Takeshi Takarada
Mesenchymal stem cell (MSC) is a type of tissue stem cell. In clinical studies, cultured MSCs have shown important therapeutic effects on diseases via the reduction of neurological defects and regulation of immune responses. However, in vivo MSC localization, function, and properties are poorly understood; therefore, the molecular understanding of MSCs hierarchy is less advanced compared to hematopoietic stem cell hierarchy. To address these issues, we developed a method that enables us to visualize MSCs, manipulate their function, and analyze their molecular biology in vivo...
2019: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Stephanie M Linker, Lara Urban, Stephen J Clark, Mariya Chhatriwala, Shradha Amatya, Davis J McCarthy, Ingo Ebersberger, Ludovic Vallier, Wolf Reik, Oliver Stegle, Marc Jan Bonder
BACKGROUND: Alternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood...
February 11, 2019: Genome Biology
Yazmin Brown, Susan Hua, Pradeep S Tanwar
The identity of cancer stem cells (CSCs) remains an enigma, with the question outstanding of whether CSCs are fixed entities or plastic cell states in response to microenvironmental cues. Recent evidence highlights the power of the tumor microenvironment to dictate CSC functionality and spatiotemporal regulation that gives rise to tumor heterogeneity. This microenvironmental regulation of CSCs parallels that of normal tissues, whereby resident stem cells reside within specialized microenvironments or 'niches', which provide the cellular and molecular signals that wire every aspect of stem cell behavior and fate...
February 8, 2019: International Journal of Biochemistry & Cell Biology
Günnur Güler, Ummu Guven, Gulperi Oktem
Current cancer treatments destroy the tumor mass but cannot prevent the recurrence of cancer. The heterogeneous structure of the tumor mass includes cancer stem cells that are responsible for tumor relapse, treatment resistance, invasion and metastasis. The biology of these cells is still not fully understood; therefore, effective treatments cannot be developed sufficiently. Herein, attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, combined with unsupervised multivariate analysis, was applied to prostate cancer stem cells (CSCs), non-stem cancer cells (non-CSCs) and normal prostate epithelial cells to elucidate the molecular mechanisms and features of CSCs, which are crucial to improving the target specific therapies...
February 11, 2019: Analyst
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