Kidney organoids: a model of the developing human

Presented by Professor Melissa Little, Murdoch Children's Research Institute, Melbourne

Mammalian kidney development has historically been studied in the mouse given the availability of the genetic and transgenic tools for interrogating the morphogenesis of this complex organ across time and space. 

While there is evidence of significant congruence in many genetic pathways between mouse and human, there are temporal, anatomical, physiological and genetic distinctions between the two species.

With the advent of efficient gene editing using CRISPR/Cas9 technology and the development of approaches for the directed differentiation of human pluripotent stem cells into models of the developing kidney, we now have an opportunity to directly investigate the genetic control of kidney morphogenesis in man. 

Kidney organoids, generated via the stepwise differentiation of such pluripotent cells to complex, multicellular 3D organoids representative of developing human tissues, completely changes the future prospects of stem cell medicine.

It is hoped that such stem cell-derived human tissue will drive personalised disease modelling, toxicity and screening, cell therapy and even tissue bioengineering. 

It is also hoped that this will provide a window into human development not previously available and potentially allow the dissection of the biophysical requirements for tissue self-organisation. 

All this will depend upon how reliably these models mirror normal human development at the level of cellular identity, multicellular complexity and functional maturation. 

Using CRISPR-Cas9 editing, we have developed a suite of reporter lines that is now allowing us to query the accuracy of patterning within the organoids, the lineage relationships during organoid formation and the transcriptional (bulk and single cell) profiles of individual cell types. 

We are also applying CRISPR-Cas9 gene editing to patient stem cell lines to test the capacity of organoids to model human kidney disease. 

Finally, the use of fluorescent reporter lines is facilitating real-time imaging after in vivo transplantation to assess the degree to which we can mature such stem cell-derived tissue for renal replacement.

Brisbane Developmental Biology Seminar

Mon 27 May 2019 3:00pm4:00pm


Large Seminar room, Level 3, QBP


Associate Professor Michael Piper