Each cell counts: Hematopoiesis and immunity research in the era of single cell genomics

Jaitin, Diego Adhemar; Keren‐Shaul, Hadas; Elefant, Naama; Amit, Ido

doi:10.1016/j.smim.2015.01.002

Cited by 36 publications

(25 citation statements)

References 69 publications

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“…Applications of these technologies to an ever increasing number of case studies have revealed that although a cell type is indeed largely characterized by differential expression of particular genes, when observed at the level of individual cells even phenotypically homogeneous cell types display a high degree of heterogeneity in the expression of individual genes. Indeed, the crucial difference between ensemble and single-cell level transcriptional assays lies resolutely in the ability to observe heterogeneity; the challenge is to interpret this heterogeneity in a meaningful way (reviewed in references 48,50,51 ).…”

Section: Single-cell Resolution Of Fate Decisionsmentioning

confidence: 99%

Transition states and cell fate decisions in epigenetic landscapes

2016

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Waddington's epigenetic landscape is an abstract metaphor frequently used to represent the relationship between gene activity and cell fates during development. Over the past few years, it has become a useful framework for interpreting results from single-cell transcriptomics experiments. It has led to the proposal that, during fate transitions, cells experience smooth, continuous progressions of global transcriptional activity, which can be captured by (pseudo)temporal dynamics. Here, focusing strictly on the fate decision events, we suggest an alternative view: that fate transitions occur in a discontinuous, stochastic manner whereby signals modulate the probability of the transition events.

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Section: Single-cell Resolution Of Fate Decisionsmentioning

confidence: 99%

Transition states and cell fate decisions in epigenetic landscapes

2016

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“…Thus, at least a thousand cells are required to guarantee the necessary power to detect such rare cell populations and states. 36 A new version of the CEL-seq protocol, called CEL-seq2, has recently been developed by the same authors and is reported to have higher sensitivity, lower costs and require even less handson time. 37 Among the key changes are the addition of UMI and the elimination of the ligation step by inserting the Illumina adaptor directly at the RT step as a 5-tail attached to the random hexamer primers.…”

Section: Cel-seq Cel-seq2 and Mars-seqmentioning

confidence: 99%

Single-cell RNA-sequencing: The future of genome biology is now

2016

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Genome-wide single-cell analysis represents the ultimate frontier of genomics research. In particular, single-cell RNA-sequencing (scRNA-seq) studies have been boosted in the last few years by an explosion of new technologies enabling the study of the transcriptomic landscape of thousands of single cells in complex multicellular organisms. More sensitive and automated methods are being continuously developed and promise to deliver better data quality and higher throughput with less hands-on time. The outstanding amount of knowledge that is going to be gained from present and future studies will have a profound impact in many aspects of our society, from the introduction of truly tailored cancer treatments, to a better understanding of antibiotic resistance and host-pathogen interactions; from the discovery of the mechanisms regulating stem cell differentiation to the characterization of the early event of human embryogenesis.

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“…However, the heterogeneity of the cells and the presence of rare cell subtypes, such as those undergoing short-lived cell fate transitions within the mixed population, make it difficult for traditional genomics approaches to identify exquisite spatiotemporal molecular changes that underlie cell fate decisions. Thus, unanswered questions arise regarding whether seemingly identical cells developing within a population exhibit similar intrinsic properties (Jaitin et al 2015;Stegle et al 2015;Trapnell 2015;Moris et al 2016). …”

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confidence: 99%

Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons

et al. 2017

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The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of developing neurons to dissect/identify NPC subtypes and critical developmental stages of alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell developmental bifurcations, tracking the stochastic transcript kinetics of the subpopulations, elucidating regulatory networks, and finding key regulators. Our data revealed the bifurcation and developmental tracks of the two NPC subpopulations, and we captured an early (24 h) transition phase that leads to alternative neuronal specifications. The consequent up-regulation and down-regulation of stageand subpopulation-specific gene groups during the course of maturation revealed biological insights with regard to key regulatory transcription factors and lincRNAs that control cellular programs in the identified neuronal subpopulations.

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Each cell counts: Hematopoiesis and immunity research in the era of single cell genomics

Cited by 36 publications

References 69 publications

Transition states and cell fate decisions in epigenetic landscapes

Transition states and cell fate decisions in epigenetic landscapes

Single-cell RNA-sequencing: The future of genome biology is now

Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons

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