scholarly journals Machine learning of stem cell identities from single-cell expression data via regulatory network archetypes

2017 ◽  
Author(s):  
Patrick S Stumpf ◽  
Ben D MacArthur
Keyword(s):  
Machine Learning ◽  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Regulatory Network ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Network Activity ◽  
Expression Data ◽  
Cell Expression

AbstractThe molecular regulatory network underlying stem cell pluripotency has been intensively studied, and we now have a reliable ensemble model for the ‘average’ pluripotent cell. However, evidence of significant cell-to-cell variability suggests that the activity of this network varies within individual stem cells, leading to differential processing of environmental signals and variability in cell fates. Here, we adapt a method originally designed for face recognition to infer regulatory network patterns within individual cells from single-cell expression data. Using this method we identify three distinct network configurations in cultured mouse embryonic stem cells – corresponding to naïve and formative pluripotent states and an early primitive endoderm state – and associate these configurations with particular combinations of regulatory network activity archetypes that govern different aspects of the cell’s response to environmental stimuli, cell cycle status and core information processing circuitry. These results show how variability in cell identities arise naturally from alterations in underlying regulatory network dynamics and demonstrate how methods from machine learning may be used to better understand single cell biology, and the collective dynamics of cell communities.

scholarly journals Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies

2017 ◽  
Vol 4 (4) ◽  
pp. 533-542 ◽  
Author(s):  
Guangdun Peng ◽  
Patrick P. L. Tam ◽  
Naihe Jing
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Developmental Process ◽  
Embryonic Stem ◽  
Molecular Signaling ◽  
Lineage Specification ◽  
Genomic Technologies ◽  
Enabling Technologies ◽  
Stem Cell Pluripotency

Abstract Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.

scholarly journals First person – Federico Pecori

2020 ◽  
Vol 133 (20) ◽  
pp. jcs255166
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Early Career ◽  
First Person ◽  
Receptor Endocytosis ◽  
Early Career Researchers ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Federico Pecori is first author on ‘Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis’, published in JCS. Federico is a PhD student in the lab of Shoko Nishihara at the Laboratory of Cell Biology, Department of Bioinformatics, Soka University, Tokyo, Japan, where he is interested in the mechanisms regulating stem cell identity.

scholarly journals Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jordi Solana ◽  
Manuel Irimia ◽  
Salah Ayoub ◽  
Marta Rodriguez Orejuela ◽  
Vera Zywitza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Alternative Splicing ◽  
Cell Biology ◽  
Embryonic Stem ◽  
In Vivo Model ◽  
Stem Cell Regulation ◽  
Specific Alternative ◽  
Functional Antagonism

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.

High-content screening of small compounds on human embryonic stem cells

2010 ◽  
Vol 38 (4) ◽  
pp. 1046-1050 ◽  
Author(s):  
Ivana Barbaric ◽  
Paul J. Gokhale ◽  
Peter W. Andrews
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
High Throughput ◽  
Cell Biology ◽  
Es Cells ◽  
Embryonic Stem ◽  
High Content Screening ◽  
Cellular Models ◽  
Compound Libraries

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

scholarly journals Gene network reconstruction using single cell transcriptomic data reveals key factors for embryonic stem cell differentiation

2019 ◽  
Author(s):  
Junil Kim ◽  
Simon Toftholm Jakobsen ◽  
Kedar Nath Natarajan ◽  
Kyoung Jae Won
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Single Cell ◽  
Regulatory Networks ◽  
Target Genes ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Expression Data

ABSTRACTGene expression data has been widely used to infer gene regulatory networks (GRNs). Recent single-cell RNA sequencing (scRNAseq) data, containing the expression information of the individual cells (or status), are highly useful in blindly reconstructing regulatory mechanisms. However, it is still not easy to understand transcriptional cascade from large amount of expression data. Besides, the reconstructed networks may not capture the major regulatory rules.Here, we propose a novel approach called TENET to reconstruct the GRNs from scRNAseq data by calculating causal relationships between genes using transfer entropy (TE). We show that known target genes have significantly higher TE values. Genes with higher TE values were more affected by various perturbations. Comprehensive benchmarking showed that TENET outperformed other GRN prediction algorithms. More importantly, TENET is uniquely capable of identifying key regulators. Applying TENET to scRNAseq during embryonic stem cell differentiation to neural cells, we show that Nme2 is a critical factor for 2i condition specific stem cell self-renewal.

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11001-11001
Author(s):  
M. M. Stevenson ◽  
W. Mostertz ◽  
C. Acharya ◽  
K. Walters ◽  
W. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Lung Adenocarcinoma ◽  
Gene Expression Data ◽  
Embryonic Stem ◽  
Cell Phenotype ◽  
Expression Data ◽  
Stem Cell Phenotype

11001 Background: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities between normal/embryonic stem cells and mature tumor cells, specific to lung cancer, are a result of underlying biologic processes, such as specific molecular pathways and regulatory networks. Methods: Using a large cohort of lung cancer cell lines with associated gene expression data, genes associated with an embryonic stem cell identity were used to develop a ‘signature’ representative of embryonic stemness (ES) activity specific to lung adenocarcinoma. Differential biology was evaluated using Gene Set Enrichment Analysis (GSEA) and signatures of oncogenic pathway deregulation. The ES signature was applied to three independent early (stage I - IIIa) lung adenocarcinoma data sets (N = 634) with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin sensitivity was also evaluated. Results: Using Bayesian regression analysis, a 100 gene signature representative of ES activity in lung adenocarcinoma was developed and validated in a leave-one-out-analysis. GSEA identified gene sets significantly represented in the ES signature: signature of neoplastic transformation, signature of undifferentiated cancer, BRCA pathway, and fibroblast serum response pathway, all associated with cancer invasiveness. Adenocarcinomas with ES demonstrated increased activation of RAS (p = 0.0002), MYC (p = 0.0057), wound healing (angiogenesis) (p < 0.0001), chromosomal instability (p < 0.0001), and invasiveness (p < 0.0001) gene signatures. Adenocarcinomas (N= 634) with ES had a decreased survival (p<0.04). The ES signature was not prognostic in prostate, ovarian, or breast adenocarcinomas. Lung tumors (N=634) and adenocarcinoma cell lines (N=31) with ES were more resistant to cisplatin (p<0.0001 and p=0.0063, respectively). Conclusions: Lung adenocarcinomas that share a common gene expression pattern with normal stem cells were associated with decreased survival and increased likelihood of resistance to cisplatin, indicating the aggressiveness of lung tumors with a stem cell phenotype. No significant financial relationships to disclose.

scholarly journals Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion

2011 ◽  
Vol 16 (3) ◽  
Author(s):  
Malgorzata Witkowska-Zimny ◽  
Edyta Wrobel
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Autologous Transplantation ◽  
Embryonic Stem ◽  
Wharton’S Jelly ◽  
Wharton's Jelly

AbstractRecently, stem cell biology has become an interesting topic, especially in the context of treating diseases and injuries using transplantation therapy. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Ideally, stem cells for regenerative medical application should be found in abundant quantities, harvestable in a minimally invasive procedure, then safely and effectively transplanted to either an autologous or allogenic host. The two main groups of stem cells, embryonic stem cells and adult stem cells, have been expanded to include perinatal stem cells. Mesenchymal stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in case of genetic disorders.This review highlights the characteristics and therapeutic potential of three human mesenchymal stem cell types obtained from perinatal sources: Wharton’s jelly, the amnion, and the chorion.

scholarly journals Optimization of mouse embryonic stem cell culture for organoid and chimeric mice production

2020 ◽  
Author(s):  
Cécilie Martin-Lemaitre ◽  
Yara Alcheikh ◽  
Ronald Naumann ◽  
Alf Honigmann
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Suspension Culture ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Model Systems ◽  
Stem Cell Culture

SummaryIn vitro stem cell culture is demanding in terms of manpower and media supplements. In recent years, new protocols have been developed to expand pluripotent embryonic stem cells in suspension culture, which greatly simplifies cell handling and scalability. However, it is still unclear how suspension culture protocols with different supplements affect pluripotency, cell homogeneity and cell differentiation compared to established adherent culture methods. Here we tested four different culture conditions for mouse embryonic stem cells (mESC) and quantified chimerism and germ line transmission as well as in vitro differentiation into three-dimensional neuro-epithelia. We found that suspension culture supplemented with CHIR99021/LIF offers the best compromise between culturing effort, robust pluripotency and cell homogeneity. Our work provides a guideline for simplifying mESC culture and should encourage more cell biology labs to use stem cell-based organoids as model systems.

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