Single cell sequencing approaches for complex biological systems.

Biological phenotype is the output of complex interactions between heterogeneous cells within a specified niche. These interactions are tightly governed and regulated by the genetic, epigenetic, and transcriptional states of single cells, with deregulation of these states resulting in disease. As such, genome wide single cell investigations are bound to enhance our knowledge of the underlying principles that govern biological systems. Recent technological advances have enabled such investigations in the form of single-cell sequencing. Here, we review the most recent developments in genome wide profiling of single cells, discuss some of the novel biological observations gleaned by such investigations, and touch upon the promise of single cell sequencing in unraveling biological systems.

[1]  John A Wolf,et al.  Transcriptome In Vivo Analysis (TIVA) of spatially defined single cells in intact live mouse and human brain tissue , 2014, Nature Methods.

[2]  Ruiqiang Li,et al.  Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells , 2013, Nature Structural &Molecular Biology.

[3]  Åsa K. Björklund,et al.  Smart-seq2 for sensitive full-length transcriptome profiling in single cells , 2013 .

[4]  Jessica C. Ebert,et al.  Accurate whole genome sequencing and haplotyping from10-20 human cells , 2012, Nature.

[5]  N. Carter,et al.  Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. , 1992, Genomics.

[6]  R. Sandberg,et al.  Full-Length mRNA-Seq from single cell levels of RNA and individual circulating tumor cells , 2012, Nature Biotechnology.

[7]  Michael Wigler,et al.  Genome-wide copy number analysis of single cells , 2012, Nature Protocols.

[8]  Åsa K. Björklund,et al.  Full-length RNA-seq from single cells using Smart-seq2 , 2014, Nature Protocols.

[9]  S. Linnarsson,et al.  Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. , 2011, Genome research.

[10]  Rong Li,et al.  Genome Analyses of Single Human Oocytes , 2013, Cell.

[11]  Kenny Q. Ye,et al.  An integrated map of genetic variation from 1,092 human genomes , 2012, Nature.

[12]  Stephen R. Quake,et al.  Genome-wide Single-Cell Analysis of Recombination Activity and De Novo Mutation Rates in Human Sperm , 2012, Cell.

[13]  Catalin C. Barbacioru,et al.  Tracing the Derivation of Embryonic Stem Cells from the Inner Cell Mass by Single-Cell RNA-Seq Analysis , 2010, Cell stem cell.

[14]  S. Linnarsson,et al.  Counting absolute numbers of molecules using unique molecular identifiers , 2011, Nature Methods.

[15]  S. P. Fodor,et al.  Counting individual DNA molecules by the stochastic attachment of diverse labels , 2011, Proceedings of the National Academy of Sciences.

[16]  T. Hashimshony,et al.  CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. , 2012, Cell reports.

[17]  I. Amit,et al.  Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types , 2014, Science.

[18]  Kun Zhang,et al.  Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells , 2013, Nature Biotechnology.

[19]  Ira M. Hall,et al.  Mosaic Copy Number Variation in Human Neurons , 2013, Science.

[20]  R. Sandberg,et al.  Deng Expression in Mammalian Cells Single-Cell RNA-Seq Reveals Dynamic , Random Monoallelic Gene , 2014 .

[21]  Aleksandra A. Kolodziejczyk,et al.  Accounting for technical noise in single-cell RNA-seq experiments , 2013, Nature Methods.

[22]  Gioele La Manno,et al.  Quantitative single-cell RNA-seq with unique molecular identifiers , 2013, Nature Methods.

[23]  Hans Lehrach,et al.  Clone-based systematic haplotyping (CSH): a procedure for physical haplotyping of whole genomes. , 2003, Genome research.

[24]  D. Evanko Two pictures are better than one , 2008, Nature Methods.

[25]  M. Metzker Sequencing technologies — the next generation , 2010, Nature Reviews Genetics.

[26]  S. Horvath,et al.  Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing , 2013, Nature.

[27]  T. Misteli Beyond the Sequence: Cellular Organization of Genome Function , 2011 .

[28]  Shintaro Katayama,et al.  SAMstrt: statistical test for differential expression in single-cell transcriptome with spike-in normalization , 2013, Bioinform..

[29]  R. Sandberg,et al.  Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells , 2014, Science.

[30]  F. Gage,et al.  RNA-sequencing from single nuclei , 2013, Proceedings of the National Academy of Sciences.

[31]  Catalin C. Barbacioru,et al.  mRNA-Seq whole-transcriptome analysis of a single cell , 2009, Nature Methods.

[32]  Pawel Zajac,et al.  Highly multiplexed and strand-specific single-cell RNA 5′ end sequencing , 2012, Nature Protocols.

[33]  J. Troge,et al.  Tumour evolution inferred by single-cell sequencing , 2011, Nature.

[34]  C. Walsh,et al.  Single-Neuron Sequencing Analysis of L1 Retrotransposition and Somatic Mutation in the Human Brain , 2012, Cell.

[35]  A. Tanay,et al.  Single cell Hi-C reveals cell-to-cell variability in chromosome structure , 2013, Nature.

[36]  Kazuki Kurimoto,et al.  An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis , 2006, Nucleic acids research.

[37]  Jie Qiao,et al.  Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing , 2012, Science.

[38]  M. Stratton,et al.  Single-cell paired-end genome sequencing reveals structural variation per cell cycle , 2013, Nucleic acids research.

[39]  Yongjun Zhao,et al.  DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution , 2012, Nature Methods.

[40]  James A. Casbon,et al.  A method for counting PCR template molecules with application to next-generation sequencing , 2011, Nucleic acids research.

[41]  Kevin A. Pelphrey,et al.  Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell , 2012 .

[42]  N. Neff,et al.  Reconstructing lineage hierarchies of the distal lung epithelium using single cell RNA-seq , 2014, Nature.

[43]  H. Ueda,et al.  Erratum to: Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity , 2017, Genome Biology.

[44]  Huanming Yang,et al.  Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor , 2012, Cell.

[45]  N. Neff,et al.  Quantitative assessment of single-cell RNA-sequencing methods , 2013, Nature Methods.

[46]  S. Kingsmore,et al.  Comprehensive human genome amplification using multiple displacement amplification , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Cole Trapnell,et al.  The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells , 2014, Nature Biotechnology.