Laboratory for Human Organogenesis
- Location：Kobe / Developmental Biology Buildings
- E-mail：minoru.takasato[at]riken.jpPlease replace [at] with @.
Directed differentiation of human PS Cells into the kidney
What is the ultimate goal of regenerative research using human pluripotent stem cells? We think this is to recreate a whole replaceable organ in vitro via directed differentiation. Due to the continuous rise in the incidence of end-stage renal disease around the world (approximately 7% per annum), there is an urgent demand for regenerative strategies to compensate for the loss of renal function in these patients. In our previous study, we developed a protocol by which human pluripotent stem cells can be differentiated into the intermediate mesoderm that can self-organize into kidney organoids. While these kidney organoids comprise all anticipated renal tissues, including nephrons, collecting duct, blood vessels and renal interstitium, they are still far from the real human kidney in terms of their size, tissue complexity, maturity and functionality. By precisely recapitulating the developmental processes of the human kidney in directed differentiation of human pluripotent stem cells, we are trying to achieve the ultimate goal of generating a three-dimensional kidney that is functional and that can also be transplanted into patients. We appreciate knowledge from basic developmental biology that is essential for such regenerative studies; therefore, we are also highly interested in studies of human embryology. Utilizing our unique technology that generates hPSC-derived kidney organoids from pluripotent stages in vitro, we are focusing particularly on uncovering the developmental mechanisms of the human mesoderm and kidney.
Kidney organoids derived from human iPS cells. The organoid contains two kidney progenitors, the ureteric tree (yellow with cyan) and nephron progenitor (red), as well as developing nephrons (yellow).
Confocal microscopic Z-stack images from the bottom to the top of kidney organoids. Developing nephrons are segmented into 4 compartments, including the collecting duct (yellow and green), distal tubule (yellow only), proximal tubule (red) and glomerulus(green only).
A schematic of kidney progenitor development in mouse embryos. The metanehpric mesenchyme (MM) and the ureteric bud (UB) are 2 kidney progenitors interacting reciprocally to build the kidney. MM is derived from the posterior intermediate mesoderm (post. IM), whereas UB emerges from the anterior IM (ant. IM). IM develops from the primitive streak (PS). We succeeded the preferential induction of either ant. IM or post IM from human iPS cells.
- Generation of functional and transplantable kidney organoids
- Investigation of developmental mechanisms of human mesoderm from hPSCs
- Developmental biology utilizing human kidney organoids as a platform
Main Publications List
- Matsubayashi M, Sakaguchi YM, Sahara Y, et al.
27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action
The FASEB Journal 35. e21262 (2020) doi: 10.1096/fj.202002077R
- Takasato M, Er P X, Chiu H S, and Little M H.
Generation of kidney organoids from human pluripotent stem cells.
Nature Protocols 11. 1681–1692 (2016) doi:10.1038/nprot.2016.098
- Takasato M, Er P X, Chiu H S, et al.
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis.
Nature 526. 564–568 (2015) doi:10.1038/nature15695
- Takasato M and Little M H.
The origin of the mammalian kidney: implications for recreating the kidney in vitro.
Development 142. 1937–1947 (2015) doi:10.1242/dev.104802
- Takasato M, Er P X, Becroft M, et al.
Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney.
Nature Cell Biology 16. 118–126 (2014) doi:10.1038/ncb2894
- Hendry C E, Vanslambrouck J M, Ineson J, et al.
Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors.
Journal of the American Society of Nephrology 24. 1424–1434 (2013) doi: 10.1681/ASN.2012121143
- Takasato M, Kobayashi C, Okabayashi K, et al.
Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development.
Biochemical and Biophysical Research Communications 373. 648–652 (2008) doi:10.1016/j.bbrc.2008.06.088