Аннотация
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.
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