title: Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire.
abstract: 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.
authors.affiliation: Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Guoji
authors.initials: G
authors.lastname: Guo
authors.forename: Sidinh
authors.initials: S
authors.lastname: Luc
authors.forename: Eugenio
authors.initials: E
authors.lastname: Marco
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Lin
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Marc A
authors.initials: MA
authors.lastname: Kerenyi
authors.forename: Semir
authors.initials: S
authors.lastname: Beyaz
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Partha Pratim
authors.initials: PP
authors.lastname: Das
authors.forename: Tobias
authors.initials: T
authors.lastname: Neff
authors.forename: Keyong
authors.initials: K
authors.lastname: Zou
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Yuan
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis* / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006413:Hematopoietic System / Q000166:cytology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D051379:Mice; D016133:Polymerase Chain Reaction; D059010:Single-Cell Analysis
chemical_list: D000954:Antigens, Surface
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