Division of Systemic Life Science

Laboratory of Molecular Cell Biology and Development

Member

KITAJIMA, TomoyaVisiting Professor

tomoya.kitajima@riken.jp See faculty
information

TAKASATO, MinoruVisiting Associate Professor

minoru.takasato@riken.jp See faculty
information

WANG, Dan OhtanVisiting Associate Professor

ohtan@riken.jp

OBATA, FumiakiVisiting Associate Professor

fumiaki.obata@riken.jp See faculty
information
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Access

Kitajima lab

RIKEN(Kobe Campus) Center for Biosystems Dynamics Research, Developmental Biology Building C

Takasato lab

RIKEN(Kobe Campus) Center for Biosystems Dynamics Research, Developmental Biology Building A

Obata lab

RIKEN(Kobe Campus) Center for Biosystems Dynamics Research, Developmental Biology Building A

WANG lab

RIKEN(Kobe Campus) Center for Biosystems Dynamics Research, Developmental Biology Building

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Kitajima lab research summary

Website of Kitajima lab

Research outline

The oocyte becomes an egg through meiosis. The egg fertilizes with a sperm and undergoes repeated cell divisions to give rise to an entire body. We study chromosome segregation during meiosis in oocytes and during mitosis in fertilized eggs, taking advantage of techniques for high-throughput and high-resolution live imaging of mouse oocytes combined with micromanipulation and genetic engineering methods. The first cell division that oocytes undergo is meiosis I. Chromosome segregation in this division is error-prone and the rate of errors increases with maternal age. Subsequently, chromosomes are segregated in meiosis II upon fertilization, and then segregated again in mitosis after DNA replication. We will reveal distinct mechanisms for chromosome segregation during these subsequent but fundamentally different cell divisions. By uncovering the mechanism of chromosome segregation during meiosis I in oocytes, we understand why oocyte meiosis I is error-prone and related to age. Comparing the mechanisms in meiosis I with those found in meiosis II and mitosis may provide insights into the capacity of cells to flexibly use different strategies for chromosome segregation. The findings will be exploited to collaborative studies with reproductive medicine.

Main themes

  • Molecular mechanisms of meiotic chromosome segregation in mouse oocytes
  • Live imaging of chromosome dynamics in oocytes
  • Aging-associated deterioration of chromosome segregation in oocytes

Takasato lab research summary

Website of Takasato lab

Research outline

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.

Main themes

  • Elucidate the mechanisms of cell fate determination of pluripotent stem cells using single-cell RNA-seq analysis.
  • Interact epithelial and mesenchymal stem cells to form organs by self-organization.
  • Direct the differentiation of human ES/iPS cells to generate 3D tissues so called “organoids” such as kidney and bladder
  • Generate kidney organoids from human iPS cells which were derived from patients with hereditary kidney disease and establish disease models.
  • Develop methods to promote vascularization and maturation of organoids to enable their application usages.

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).

Movie of research introduction

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).

WANG lab research summary

Website of WANG lab

Research outline

Functional genomics and systems biology have opened new doors to previously inaccessible genomic information and holistic approaches to study complex networks of genes and proteins in the central nervous system. The advances are revolutionizing our understanding of the genetic underpinning of cognitive development and decline by facilitating identifications of novel molecular regulators and physiological pathways underlying brain function, and by associating polymorphism and mutations to cognitive dysfunction and neurological diseases. However, our current understanding of these complex gene regulatory mechanisms has yet lacked sufficient mechanistic resolution for further translational breakthroughs. We are currently studying the burgeoning field of epitranscriptomics on chemical modifications of RNA molecules in association of cognitive functions. The new evidence is suggesting that this new layer of RNA regulation may be of particular interest for the spatiotemporally coordinated regulation of gene networks in the developing and declining brain and underlies the structural and functional correlates of cognitive changes.

Main themes

  • Synaptic epitranscriptome
  • Understanding physiological functions of mRNA chemical modification
  • Dynamic RNA chemical modification during aging

Obata lab research summary

Website of Obata lab

Research outline

All animals require constant nutrition from their diet as they grow and age. Our healthspan is greatly influenced by the dietary environment. Diet contributes to the metabolic and physiological homeostasis of animals directly as nutrients or indirectly via gut bacteria, but our understanding of the detailed molecular mechanisms is limited. Our laboratory studies the physiological functions of various nutrients and gut bacteria. We are also trying to elucidate the mechanisms by which transient dietary intake during development influences health status throughout life. We use the short-lived fruit fly Drosophila melanogaster to elucidate the universal “dietological” mechanisms that regulate the ageing and lifespan of organisms.

Our research focuses on lifespan as an indicator of an individual’s overall capacity for homeostasis. We need to carefully unravel the mechanisms of how and which factors determine lifespan. In conducting research on ageing, it is reasonable to use simpler organisms with shorter life spans. We use cheap, handy, and a sophisticated genetic model Drosophila, which has a lifespan of only two months. It has few ethical problems and is ideal for life-span measurements, which requires a huge number of animals. Therefore, Drosophila as a simple model organism, is the best tool to understand the universal and fundamental mechanisms of the organism.

Until now, biomedical studies seem to have aimed at how to cure and/or avoid disease. However, being healthy and not being sick are similar but different. It seems to us that living organisms inherently have the power to try to become healthy. In our research, we are trying to clarify the basic mechanisms of homeostasis.

Main themes

  • Elucidation of functions of each nutrient and gut bacterial species
  • Elucidation of the mechanism by which early life environment alters homeostasis
  • Elucidation of the amino acid regulation of healthspan
  • Molecular basis of thermotolerance
  • Molecular basis of feeding/blood feeding