LifeMap Discovery™: The Embryonic Development, Stem Cells, and Regenerative Medicine Research Portal

Edgar, Ron; Mazor, Yaron; Rinon, Ariel; Blumenthal, Jacob B.; Golan, Yaron; Buzhor, Ella; Livnat, Idit; Ben‐Ari, Shani; Lieder, Iris; Shitrit, Alina; Gilboa, Yaron; Ben‐Yehudah, Ahmi; Edri, Osnat; Shraga, Netta; Bogoch, Yoel; Leshansky, Lucy; Aharoni, Shlomi; West, Michael; Warshawsky, David; Shtrichman, Ronit

doi:10.1371/journal.pone.0066629

Cited by 92 publications

(95 citation statements)

References 28 publications

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“…We applied two complementary approaches to interpret these clusters: i) a comparison with gene expression signatures obtained from hESCs in their undifferentiated state or upon differentiation towards the three major germ layers; and ii) gene ontology enrichment analysis for both biological processes and developmental cell identity (Edgar et al, 2013) (Figure S2D; representative genes in Figure 3B and Figure S2B). …”

Section: Resultsmentioning

confidence: 99%

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency

Cacchiarelli

Trapnell

Ziller

et al. 2015

Cell

205

284

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Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies.

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Section: Resultsmentioning

confidence: 99%

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency

Cacchiarelli

Trapnell

Ziller

et al. 2015

Cell

205

284

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“…Differentially expressed genes were then grouped into those with shared and unique expression profiles (Figure 4C). Such expression patterns were further subjected to gene ontology analysis (Edgar et al, 2013) (Figure 4D). Genes associated with extracellular matrix reorganization were significantly enriched in all non-CNS derived cell types.…”

Section: Resultsmentioning

confidence: 99%

“…Reads were then counted using HTseq (Anders et al, 2015) and differentially expressed genes were calculated using DESeq (Anders and Huber, 2010). Differentially expressed groups analyzed for their gene ontology classification and signaling pathway enrichment using LifeMap Gene Analytics (Edgar et al, 2013). Resulting RNA sequencing datasets are uploaded to GEO (GSE101661) and significant differentially expressed gene sets are in Supplemental Table 1.…”

Section: Methods Detailsmentioning

confidence: 99%

A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages

et al. 2017

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SUMMARY Directing the fate of human pluripotent stem cells (hPSCs) into different lineages requires variable starting conditions and components with undefined activities, introducing inconsistencies that confound reproducibility and assessment of specific perturbations. Here we introduce a simple, modular protocol for deriving the four main ectodermal lineages from hPSCs. By precisely varying FGF, BMP, WNT, and TGFβ pathway activity in a minimal, chemically-defined medium, we show parallel, robust, and reproducible derivation of neuroectoderm, neural crest (NC), cranial placode (CP), and non-neural ectoderm in multiple hPSC lines, on different substrates independently of cell density. We highlight the utility of this system by interrogating the role of TFAP2 transcription factors in ectodermal differentiation, revealing the importance of TFAP2A in NC and CP specification, and performing a small molecule screen that identified compounds which further enhance CP differentiation. This platform provides a simple stage for systematic derivation of the entire range of ectodermal cell types.

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“…In addition, the section contains (i) a link to a search of the disease name within the NIH clinical center (http://clinicalcenter.nih.gov/), yielding additional information regarding clinical trials; (ii) Cell-based therapeutic approaches from LifeMap Discovery (16), which include stem-cell-based therapeutics, and Embryonic/adult cultured cells (candidate therapeutic approaches); and (iii) a link to Mesh lookup in the Cochrane library of evidence-based medicine (17), which provides evidence enabling informed healthcare decision-making.…”

Section: Annotationsmentioning

confidence: 99%

“…Finally, MalaCards shows in the Anatomical Context section several data entries related to more detailed disease-tissue relationships. These include the in-house MalaCards organs/tissues relations selected from a broader repertoire of 82 anatomical entities, obtained by extensive text mining of individual cards; Foundational Model of Anatomy (FMA) ontology data connected to the disease via DO; Assignment of the cells, compartments, and organs relevant to the disease, obtained from LifeMap Discovery (16). …”

Section: Annotationsmentioning

confidence: 99%

MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search

et al. 2016

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The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across often-conflicting sources, providing effective annotation consolidation. A central feature is a balanced Genes section, with scores reflecting the strength of disease-gene associations. This is accompanied by other gene-related disease information such as pathways, mouse phenotypes and GO-terms, stemming from MalaCards’ affiliation with the GeneCards Suite of databases. MalaCards’ capacity to inter-link information from complementary sources, along with its elaborate search function, relational database infrastructure and convenient data dumps, allows it to tackle its rich disease annotation landscape, and facilitates systems analyses and genome sequence interpretation. MalaCards adopts a ‘flat’ disease-card approach, but each card is mapped to popular hierarchical ontologies (e.g. International Classification of Diseases, Human Phenotype Ontology and Unified Medical Language System) and also contains information about multi-level relations among diseases, thereby providing an optimal tool for disease representation and scrutiny.

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LifeMap Discovery™: The Embryonic Development, Stem Cells, and Regenerative Medicine Research Portal

Cited by 92 publications

References 28 publications

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency

A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages

MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search

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