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髙里 実チームリーダーの写真

Team Leader
Minoru Takasato Ph.D.

Laboratory for Human Organogenesis

LocationKobe / Developmental Biology Buildings

E-mailminoru.takasato[at]riken.jp

Please replace [at] with @.

Recapitulating human organogenesis to generate organoids from human pluripotent stem cells

What do you think is the ultimate goal of regenerative research using human pluripotent stem cells? We think that is to recreate a whole replaceable organ in vitro via directed differentiation. In the previous study, we developed a protocol by which human pluripotent stem cells can be differentiated into the intermediate mesoderm that self-organizes kidney organoids. Kidney organoids comprises all anticipated renal tissues, including nephrons, collecting duct, blood vessels and renal interstitium, although, they are still far from the real human kidney in their size, tissue complexity, maturity and functionality. By precisely recapitulating the developmental process of human kidney in directed differentiation of human pluripotent stem cells, we are trying to achieve the ultimate goal, generation of a three-dimensional urinary tract including the kidney and the bladder that is functional and transplantable to the patients. We also study about how to recapitulate the development of other organs that connect to the kidney. We appreciate knowledge from basic developmental biology that is essential for such regenerative studies; therefore, we are highly interested in studies of human embryology. Utilizing our unique technology that generates hPSCs-derived kidney organoids from the pluripotent stage in vitro, we are especially investigating developmental mechanisms of 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.

Research Theme

  • Generation of functional and transplantable urinary tract organoids
  • Investigation of developmental mechanisms of human mesendoderm from hPSCs
  • Developmental biology utilizing human organoids as a platform

Selected Publications

Matsubayashi M, Sakaguchi YM, Sahara Y, et al.
27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.
FASEB Journal 35(1), e21262 Fri Jan 01 00:00:00 JST 2021 doi: 10.1096/fj.202002077R

Knarston IM, Pachernegg S, Robevska G, et al.
An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development.
Stem Cell Reports 15(6), 1377-1391 Tue Dec 08 00:00:00 JST 2020 doi: 10.1016/j.stemcr.2020.10.009

Yamamura T, Horinouchi T, Adachi T, et al.
Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5.
Nature Communications 11(1), 2777 Tue Jun 02 00:00:00 JST 2020 doi: 10.1038/s41467-020-16605-x

Takasato M, Wymeersch FJ.
Challenges to future regenerative applications using kidney organoids.
Curr. Opin. Biomed. Eng. 13, 144-151 Fri Jan 31 00:00:00 JST 2020 doi: 10.1016/j.cobme.2020.03.003

Takasato M.
Advice for the Next Generation: Minoru Takasato.
Cell Stem Cell 24, 688-689 Sun Dec 01 00:00:00 JST 2019 doi: 10.1016/j.stem.2019.04.009

Phipson B, Er PX, Combes AN, et al.
Evaluation of variability in human kidney organoids.
Nature Methods 16(1), 79-87 Tue Jan 01 00:00:00 JST 2019 doi: 10.1038/s41592-018-0253-2

van den Berg CW, Ritsma L, Avramut MC, et al.
Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo.
Stem Cell Reports 10(3), 751-765 Tue Mar 13 00:00:00 JST 2018 doi: 10.1016/j.stemcr.2018.01.041

Takasato M, Er P X, Chiu H S, Little M H.
Generation of kidney organoids from human pluripotent stem cells.
Nature Protocols 11, 1681-1692 Thu Dec 01 00:00:00 JST 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 Tue Dec 01 00:00:00 JST 2015 doi: 10.1038/nature15695

Takasato M, Little M H.
The origin of the mammalian kidney: implications for recreating the kidney in vitro.
Development 142, 1937-1947 Sun Nov 01 00:00:00 JST 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 Mon Dec 01 00:00:00 JST 2014 doi: 10.1038/ncb2894

Members

Minoru Takasato

Team Leader

Wei Zhao

Research Scientist

Filip Jos Wymeersch

Research Scientist

Junichi Taniguchi

Special Postdoctoral Researcher

Olena Trush

Research Scientist

Yoshiki Sahara

Visiting Scientist

Chie Fukui

Technical Staff I

Kensuke Yabuuchi

Research Associate

Kazuhiro Ofuji

Research Associate

Rio Noto

Student Trainee

Wataru Uno

Junior Research Associate

Yukari Usuda

Student Trainee

Taiki Satoh

Junior Research Associate

Masaya Goto

Student Trainee

Eri Yamashita

Administrative Part-time Worker I

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