(A) Alternative
splicing patterns
of CD45 during T-cell activation. Isoforms (CD45RA, CD45RB, CD45R0)
with decreasing exon inclusion were expressed upon T-cell activation.
(B) The procedures of SpliceRCA for detecting splice variants in single
cells. The splice-junction anchored padlock probe is composed of four
modules: the recognition of exon junction sites (Rx, Ry), universal
priming region (P), and tag motif (T) modules. The newly formed splice
junction in the target splice isoform brings close proximity between
Rx and Ry in the padlock probe for circularizing, following primer
hybridized with the P, triggering in situ RCA. Upon
tuning of the sequence of T corresponding to different fluorophores,
the three RNA splicing variants can thus be simultaneously differentiated,
and visualized with single-molecule resolution attributed to the in situ one-target-one-amplicon amplification method.