Wagner DE, Weinreb C, Zollins ZM, Briggs JA, Megason SG, Klein AM. Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo. Science. 2018;Epubc.
Weinreb C, Wolock S, Klein AM. SPRING: a kinetic interface for visualizing high dimensional single-cell expression data. Bioinfomatics. 2018;34 (7) :1246-8.
Briggs JA, Weinreb C, Wagner DE, Megason S, Peshkin L, Kirschner MW, Klein AM. The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution. Science. 2018;Epub.
Raj B, Wagner DE, McKenna A, Pandey S, Klein AM, Shendure J, Gagnon JA, Schier AF. Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain. Nat Biotechnol. 2018;Epub.
Tusi BK, Wolock SL, Weinreb C, Hwang Y, Hildalgo D, Zilionis R, Waisman A, Huh JR, Klein AM, Socolovsky M. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018;555 (7694) :50-64.
Weinreb C, Wolock S, Tusi BK, Socolovsky M, Klein AM. Fundamental limits on dynamic inference from single-cell snapshots. Proc Natl Acad Sci U S A. 2018;115 (10) :E2467-E2476.
Rodriguez-Fraticelli AE, Wolock SL, Weinreb CS, Panero R, Patel SH, Jankovic M, Sun J, Calogero RA, Klein AM, Camargo FD. Clonal analysis of lineage fate in native haematopoiesis. Nature. 2018;553 (7687) :212-16.
Hrvatin S, Hochbaum DR, Nagy MA, Cicconet M, Robertson K, Cheadle L, Zillionis R, Ratner A, Borges-Monroy R, Klein AM, et al. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neuro Science. 2018;21 (1) :120-129.
Zemmour D, Zillionis R, Kiner E, Klein AM, Mathis D, Benoist C. Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nat Immunol. 2018;19 (3) :291-301.
Briggs, J, Li, VC, Lee, S, Woolf, C, Klein, AM, Kirschner, M. Mouse embryonic stem cells can differentiate via multiple paths to the same state . bioRxiv [Internet]. 2017. Publisher's Version
Weinreb, C, Wolock, SL, Tusi, BK, Socolovsky, M, Klein, AM. Fundamental limits on dynamic inference from single cell snapshots . bioRxiv [Internet]. 2017. Publisher's Version
Mesa, KR, Kawaguchi, K, Gonzalez, D, Cockburn, K, Boucher, J, Xin, T, Klein, AM, Greco V. Epidermal stem cells self-renew upon neighboring differentiation. bioRxiv [Internet]. 2017. Publisher's Version
Klein, AM, Macosko, E. InDrops and Drop-seq technologies for single-cell sequencing. Lab Chip. 2017;17 (15).
Wagner, BK, Klein AM. Genetic screening enters the single-cell era. . Nature Methods. 2017;14 (3) :237-38.
Zilionis R, Nainys J, Veres A, Savova V, Zemmour D, Klein AM, L. M. Single-cell barcoding and sequencing using droplet microfluidics. Nature Protocols. 2017;12 (1) :44-73.
Baron, M, Veres, A, Wolock, SL, Faust, AL, Gaujoux, R, Vetere, A, Yu R, Wagner, BK, Shen-Orr, SS, Klein, AM, et al. single-Cell Transciptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure. . Cell Systems. 2016;4712 (16).
Derr, A, Yang, C, Zilionis, R, Sergushichev, A, Blodgett, DM, Redick, S, Bortell, R, Luban, J, Harlan, DM, Kadener, S, et al. End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data. Genome Res . 2016;26 (10) :1397-1410.
Rompolas, P, Mesa, KR, Kawaguchi, K, Park, D, Gonzalez, D, Brown, S, Boucher, J, Klein, AM, Greco V. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis. Science. 2016;352 (6292) :Epub.
Peshkin, L, Wühr, M, Pearl, E, Haas, W, Freeman, RM Jr, Gerhart, JC, Klein, AM, Horb, M, Gygi, SP, Kirschner MW. On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development. Developmental Cell. 2015;35 (33) :383-94.
Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell. 2015;161 (5) :1187-201.Abstract
It has long been the dream of biologists to map gene expression at the single-cell level. With such data one might track heterogeneous cell sub-populations, and infer regulatory relationships between genes and pathways. Recently, RNA sequencing has achieved single-cell resolution. What is limiting is an effective way to routinely isolate and process large numbers of individual cells for quantitative in-depth sequencing. We have developed a high-throughput droplet-microfluidic approach for barcoding the RNA from thousands of individual cells for subsequent analysis by next-generation sequencing. The method shows a surprisingly low noise profile and is readily adaptable to other sequencing-based assays. We analyzed mouse embryonic stem cells, revealing in detail the population structure and the heterogeneous onset of differentiation after leukemia inhibitory factor (LIF) withdrawal. The reproducibility of these high-throughput single-cell data allowed us to deconstruct cell populations and infer gene expression relationships. VIDEO ABSTRACT.