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Publication : Single cell dissection of early kidney development: multilineage priming.

First Author  Brunskill EW Year  2014
Journal  Development Volume  141
Issue  15 Pages  3093-101
PubMed ID  25053437 Mgi Jnum  J:214091
Mgi Id  MGI:5588052 Doi  10.1242/dev.110601
Citation  Brunskill EW, et al. (2014) Single cell dissection of early kidney development: multilineage priming. Development 141(15):3093-101
abstractText  We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction.
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