Mapping Cellular Hierarchy by Single-Cell Analysis of the Cell Surface Repertoire

被引：185

作者：

Guo, Guoji ^{[1
,2
]}

Luc, Sidinh ^{[1
,2
]}

Marco, Eugenio ^{[4
]}

Lin, Ta-Wei ^{[5
]}

Peng, Cong ^{[1
,2
]}

Kerenyi, Marc A. ^{[1
,2
]}

Beyaz, Semir ^{[1
,2
]}

Kim, Woojin ^{[1
,2
]}

Xu, Jian ^{[1
,2
]}

Das, Partha Pratim ^{[1
,2
]}

Neff, Tobias ^{[6
]}

Zou, Keyong ^{[7
]}

Yuan, Guo-Cheng ^{[4
]}

Orkin, Stuart H. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[5] Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA

[6] Univ Colorado, Pediat Hematol Oncol BMT, Aurora, CO 80045 USA

[7] Boston Open Labs, Cambridge, MA 02138 USA

来源：

CELL STEM CELL | 2013年 / 13卷 / 04期

基金：

美国国家卫生研究院;

关键词：

HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION ANALYSIS; ACUTE MYELOID-LEUKEMIA; MOUSE BONE-MARROW; MESSENGER-RNA-SEQ; TRANSCRIPTION FACTOR; PROGENITOR CELLS; IDENTIFICATION; GATA-1; LINEAGES;

D O I：

10.1016/j.stem.2013.07.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：492 / 505

页数：14

共 41 条

[1] Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].