Kidney development - Little Group

The Little Group aims to direct stem cells to kidney organoids.

Research focus

Our laboratory generates models of the human kidney using pluripotent stem cells. Our seminal study in 2015 (Takasato et al, Nature) described an approach for generating kidney organoids containing appropriately patterned and segmented nephrons, surrounding renal stroma, endothelial and perivascular cell populations.

We have fully characterised the cellular components within kidney organoids and shown that our protocol is robust, reproducible, and transferable across different pluripotent stem cell lines. Using these human kidney tissues, we hope to develop new therapies for kidney disease.

Our research includes the modelling of genetic forms of kidney disease for drug development and the engineering of kidney tissue to ultimately deliver renal replacement.

Main research projects

Factorial analysis of lineage commitment during kidney organoid differentiation
Investigating the impact of stroma on kidney organoid specification and patterning
Investigating the impact of tension on ureteric epithelial commitment
Proteomic characterization of podocin mistrafficking in a model of congenital nephrotic syndrome

Selected publications

List of publications by Melissa Little

Takasato M, Er P, Chiu H, Maier B, Baillie G, Ferguson C, Parton R, Wolvetang E, Roost MS, Chuva de Sousa Lopes SM, Little MH. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature (2015) 526(7574): 564-568 (front cover). DOI: 10.1038/nature15695
Takasato M, Er PX, Becroft M, Vanslambrouck JM, Stanley EG, Elefanty AG, Little MH. Directing human embryonic stem cell differentiation towards a renal lineage generates a self- organising kidney. Nature Cell Biology (2014) 16(1):118-26. (front cover). DOI: 10.1038/ncb2894
Lawlor KT, Vanslambrouck JM, Higgins W, Chambon A, Bishard K, Arndt D, Er PX, Wilson S, Howden SE, Tan KS, Li F, Hale LJ, Shepherd B, Pentoney S, Presnell SC, Chen AE, Little MH. Cellular extrusion bioprinting improves kidney organoid throughput, scale reproducibility and conformation. Nature Materials (2021);20(2):260-271.DOI: 10.1038/s41563-020-00853-9
Phipson B, Er PX, Combes AN, Forbes TA, Howden SE, Zappia L, Yen HJ, Lawlor KT, Hale LJ, Sun J, Wolvetang E, Takasato M, Oshlack A, Little MH. Evaluation of variability in human kidney organoids. Nature Methods (2019) 16(1):79-87. DOI: 10.1038/s41592-018-0253-2
Forbes TA, Howden SE, Lawlor K, Phipson B, Maksimovic J, Hale L, Wilson S, Quinlan C, Ho G, Holman K, Bennetts B, Crawford J, Trnka P, Oshlack A, Patel C, Mallett A, Simons C, Little MH. Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renalphenotype and reveal underlying pathogenetic mechanisms. Am J Hum Genet. (2018) 102(5): 816-831. DOI: 10.1016/j.ajhg.2018.03.014