FigureĀ 2.
A broad timeline of single-cell functional, molecular, and computational techniques. Although clonal functional assays have developed slowly over many decades, global single-cell molecular profiling (and its associated analytical tools) have been largely developed in the last 10 years. The pace of these developments and the breadth of competing/complementary tools makes it more challenging to navigate. The Venn diagram (bottom-left) depicts each tool and identifies the aspects of HSC biology that can be assessed via each technique (cellular function, molecular profile, or clonal tracking). In addition to these individual limitations, it is important to note that most multiomic techniques are not as robust as singleomic techniques optimized to capture 1 molecular aspect, and these combinatorial technologies should be used with great caution. ATAC-seq, assay for transposase-accessible chromatin sequencing; G&T-seq, genome and transcriptome sequencing; NEAT-seq, sequencing of nuclear protein epitope abundance, chromatin accessibility and the transcriptome in single cells; qPCR, quantitative polymerase chain reaction; sc-assays, single-cell assays; sci-CAR, single-cell combinatorial indexing-based coassay that jointly profiles chromatin accessibility and mRNA; scM&T-seq, single-cell methylome and transcriptome sequencing; scNMT-seq, single-cell nucleosome, methylation and transcription sequencing.

A broad timeline of single-cell functional, molecular, and computational techniques. Although clonal functional assays have developed slowly over many decades, global single-cell molecular profiling (and its associated analytical tools) have been largely developed in the last 10 years. The pace of these developments and the breadth of competing/complementary tools makes it more challenging to navigate. The Venn diagram (bottom-left) depicts each tool and identifies the aspects of HSC biology that can be assessed via each technique (cellular function, molecular profile, or clonal tracking). In addition to these individual limitations, it is important to note that most multiomic techniques are not as robust as singleomic techniques optimized to capture 1 molecular aspect, and these combinatorial technologies should be used with great caution. ATAC-seq, assay for transposase-accessible chromatin sequencing; G&T-seq, genome and transcriptome sequencing; NEAT-seq, sequencing of nuclear protein epitope abundance, chromatin accessibility and the transcriptome in single cells; qPCR, quantitative polymerase chain reaction; sc-assays, single-cell assays; sci-CAR, single-cell combinatorial indexing-based coassay that jointly profiles chromatin accessibility and mRNA; scM&T-seq, single-cell methylome and transcriptome sequencing; scNMT-seq, single-cell nucleosome, methylation and transcription sequencing.

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