Atlas of Gene Expression in the Developing Kidney at Microanatomic Resolution

Brunskill, Eric W.; Aronow, Bruce J.; Georgas, Kylie; Rumballe, Bree; Valerius, M. Todd; Aronow, Jeremy; Kaimal, Vivek; Jegga, Anil G.; Yu, Jing; Grimmond, Sean M.; McMahon, Andrew P.; Patterson, Larry T.; Little, Melissa H.; Potter, S. Steven

doi:10.1016/j.devcel.2009.02.014

Cited by 19 publications

(31 citation statements)

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“…3i and Supplementary Videos 3 and 4), a feature never observed in explanted embryonic mouse kidneys 21 . Finally, nephrons were surrounded by MEIS1 1 renal interstitial cells 22 , some of which were also FOXD1 1 (Fig. 3j and Extended Data Fig.…”

Section: Research Lettermentioning

confidence: 97%

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Takasato

Chiu

et al. 2015

Nature

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The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.

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Section: Research Lettermentioning

confidence: 97%

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Takasato

Chiu

et al. 2015

Nature

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1,290

1,427

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“…Global gene profiling during kidney development has provided novel insights into the genetic program that controls murine and human nephrogenesis and sets a reference for abnormal nephrogenesis [25][26][27][28][29][30]. Accordingly, Dekel et al demonstrated that the overall gene expression profile of a WT specimen was most similar to that observed for an 8-week human gestation kidney and not later gestation kidneys [29].…”

Section: Genomic Microarray Studiesmentioning

confidence: 98%

Wilms tumor—a renal stem cell malignancy?

Pode‐Shakked

Dekel

2011

Pediatr Nephrol

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Wilms' tumor (WT; nephroblastoma) is the most common pediatric renal malignancy and rated fourth in overall incidence among childhood cancers. It is viewed as a prototype of differentiation failure in human neoplasia as it recapitulates the histology of the nephrogenic zone of the growing fetal kidney. The cellular origin of WT is unclear. However, recent genomic, genetic and epigenetic studies point to an early renal stem/progenitor cell that undergoes malignant transformation as the source for WT. In this context, classical WT shares genes and pathways activated in progenitors committed to the renal lineage. However, direct proof and characterization of the WT initiating cell have remained elusive. Novel methodologies recently adopted from the cancer stem cell scientific field, including the analysis of sorted single human tumor cells, have been applied to WT. These have enabled the identification of cell sub-populations that show similarities-in terms of molecular marker expression-to human fetal kidney progenitors and are, therefore, likely to be derivatives of the same lineage. Further elucidation of the WT cancer stem cell or the cell of origin in human tumors and in transgenic mouse models that generate murine tumors may not only provide novel therapeutic targets but also shed light on the normal kidney stem cell.

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“…Further, there is the interstitium, or stroma, which can be divided into cortical and medullary regions. By using primarily laser capture microdissection it was possible to purify 15 distinct compartments of the developing kidney and then to use microarrays to generate global gene expression profiles [11]. Several interesting principles emerged from the analysis of this compartment-specific atlas of gene expression of the developing kidney.…”

Section: An Atlas Of Gene Expression In the Developing Kidneymentioning

confidence: 99%

“…The promoter regions of genes with elevated expression in a particular compartment can be examined for the presence of evolutionarily conserved transcription factor binding sites, thereby defining a regulatory signature. In this manner it is possible to begin to decipher the genetic interactions, which genes regulate which, during kidney development [11].…”

Section: An Atlas Of Gene Expression In the Developing Kidneymentioning

confidence: 99%

“…The arrays provide a global definition of the waves of gene expression that occur as development proceeds. Bioinformatics analysis can identify, for example, the top thousand genes that change in expression for each stage, from capping mesenchyme to renal vesicle, from renal vesicle to S-shaped body, and so on [11].…”

Section: An Atlas Of Gene Expression In the Developing Kidneymentioning

confidence: 99%

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Defining the genetic blueprint of kidney development

2011

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Thousands of genes show differential expression patterns during kidney development, suggesting that the genetic program driving this process is complex. While great progress has been made in defining the outline of the genetic basis of nephrogenesis, it is clear that much remains to be learned. A global atlas of the gene expression profiles of the multiple elements of the developing kidney would allow the identification of novel growth factor-receptor interactions, identify additional molecular markers of distinct components, facilitate the generation of compartment specific GFP-CRE transgenic mouse tools, lend insights into the genetic regulatory circuits governing nephron formation, and fully characterize the waves of gene expression that impel nephrogenesis. Both microarrays and next generation deep sequencing of cDNA libraries can be used to define comprehensive, sensitive, and quantitative gene expression profiles. In addition, laser capture microdissection and transgenic GFP mice can be used to isolate specific compartments and pure cell types from the developing kidney. Advancing technologies are even allowing robust gene expression profiling of single cells. The final goal is the production of an exquisitely detailed atlas of the gene expression program that drives kidney development.

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Atlas of Gene Expression in the Developing Kidney at Microanatomic Resolution

Cited by 19 publications

References 0 publications

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Wilms tumor—a renal stem cell malignancy?

Defining the genetic blueprint of kidney development

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