title: Single cell dissection of early kidney development: multilineage priming.
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 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.
authors: Division of Developmental Biology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors: Eric W
authors: EW
authors: Brunskill
authors: Division of Urology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors: Joo-Seop
authors: JS
authors: Park
authors: Division of Urology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors: Eunah
authors: E
authors: Chung
authors: Department of Internal Medicine/Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA.
authors: Feng
authors: F
authors: Chen
authors: Division of Developmental Biology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors: Bliss
authors: B
authors: Magella
authors: Division of Developmental Biology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA steve.potter@cchmc.org.
authors: S Steven
authors: SS
authors: Potter
mesh_terms: D000818:Animals; D019070:Cell Lineage; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007668:Kidney / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D009399:Nephrons / Q000196:embryology; D038081:Organogenesis / Q000235:genetics; D050199:Podocytes / Q000166:cytology; D012313:RNA / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D022661:RNA, Untranslated; D049452:Green Fluorescent Proteins; D012313:RNA
keywords: Kidney development; Mouse; Multilineage priming; Single cell analysis