Single-cell transcriptional analysis of neuronal progenitors.
The extraordinary cellular heterogeneity of the mammalian nervous system has largely hindered the molecular analysis of neuronal identity and diversity. In order to uncover mechanisms involved in neuronal differentiation and diversification, we have monitored the expression profiles of individual neurons and progenitor cells collected from dissociated tissue or captured from intact slices. We demonstrate that this technique provides a sensitive and reproducible representation of the single-cell transcriptome. In the olfactory system, hundreds of transcriptional differences were identified between olfactory progenitors and mature sensory neurons, enabling us to define the large variety of signaling pathways expressed by individual progenitors at a precise developmental stage. Finally, we show that regional differences in gene expression can be predicted from transcriptional analysis of single neuronal precursors isolated by laser capture from defined areas of the developing brain.
Tietjen
Ian
I
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Rihel
Jason M
JM
Cao
Yanxiang
Y
Koentges
Georgy
G
Zakhary
Lisa
L
Dulac
Catherine
C
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007834:Lasers; D051379:Mice; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology / Q000294:innervation; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C065500:ASCL1 protein, human; C499317:Ascl1 protein, mouse