Single cell dissection of early kidney development: Multilineage priming

Eric W. Brunskill, Joo Seop Park, Eunah Chung, Feng Chen, Bliss Magella, S. Steven Potter

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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 readthrough 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.

Original languageEnglish
Pages (from-to)3093-3101
Number of pages9
JournalDevelopment (Cambridge)
Volume141
Issue number15
DOIs
StatePublished - Aug 2014

Keywords

  • Kidney development
  • Mouse
  • Multilineage priming
  • Single cell analysis

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    Brunskill, E. W., Park, J. S., Chung, E., Chen, F., Magella, B., & Potter, S. S. (2014). Single cell dissection of early kidney development: Multilineage priming. Development (Cambridge), 141(15), 3093-3101. https://doi.org/10.1242/dev.110601