Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire

Guo, G., Luc, S., Marco, E., Lin, T. W., Peng, C., Kerenyi, M. A., Beyaz, S., Kim, W., Xu, J., Das, P. P., Neff, T., Zou, K., Yuan, G. C., Orkin, S. H. (October 2013) Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire. Cell Stem Cell, 13 (4). pp. 492-505. ISSN 1875-9777 (Electronic)1875-9777 (Linking)

DOI: 10.1016/j.stem.2013.07.017


Stem cell differentiation pathways are most often studied at the population level, whereas critical decisions are executed at the level of single cells. We have established a highly multiplexed, quantitative PCR assay to profile in an unbiased manner a panel of all commonly used cell surface markers (280 genes) from individual cells. With this method, we analyzed over 1,500 single cells throughout the mouse hematopoietic system and illustrate its utility for revealing important biological insights. The comprehensive single cell data set permits mapping of the mouse hematopoietic stem cell differentiation hierarchy by computational lineage progression analysis. Further profiling of 180 intracellular regulators enabled construction of a genetic network to assign the earliest differentiation event during hematopoietic lineage specification. Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct cellular hierarchy containing two independent self-renewing lineages with different clonal activities. The strategy has broad applicability in other cellular systems.

Item Type: Paper
Uncontrolled Keywords: Animals Antigens, Surface/*analysis/*genetics Cell Differentiation/genetics Cell Lineage/genetics Hematopoietic Stem Cells/cytology/metabolism Hematopoietic System/cytology Humans Leukemia, Myeloid, Acute/genetics/pathology Mice Polymerase Chain Reaction *Single-Cell Analysis
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation
Investigative techniques and equipment > cell lineage tracing
CSHL Authors:
Communities: CSHL labs > Beyaz lab
Depositing User: Matt Covey
Date: 3 October 2013
Date Deposited: 01 Feb 2018 22:00
Last Modified: 01 Feb 2018 22:00
PMCID: PMC3845089
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