The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform

Shin Ichi Mae - One of the best experts on this subject based on the ideXlab platform.

  • Efficient and rapid induction of human iPSCs/ESCs into nephrogenic intermediate mesoderm using small molecule-based differentiation methods.
    PloS one, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

  • efficient and rapid induction of human ipscs escs into nephrogenic intermediate mesoderm using small molecule based differentiation methods
    PLOS ONE, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

  • monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells
    Nature Communications, 2013
    Co-Authors: Shin Ichi Mae, Akemi Shono, Fumihiko Shiota, Tetsuhiko Yasuno, Masatoshi Kajiwara, Nanaka Gotodanishimura, Sayaka Arai, Aiko Satootubo, Taro Toyoda, Kazutoshi Takahashi
    Abstract:

    A method for stimulating the differentiation of human pluripotent stem cells into kidney lineages remains to be developed. Most cells in kidney are derived from an Embryonic Germ Layer known as intermediate mesoderm. Here we show the establishment of an efficient system of homologous recombination in human pluripotent stem cells by means of bacterial artificial chromosome-based vectors and single-nucleotide polymorphism array-based detection. This system allowed us to generate human-induced pluripotent stem cell lines containing green fluorescence protein knocked into OSR1, a specific intermediate mesoderm marker. We have also established a robust induction protocol for intermediate mesoderm, which produces up to 90% OSR1(+) cells. These human intermediate mesoderm cells can differentiate into multiple cell types of intermediate mesoderm-derived organs in vitro and in vivo, thereby supplying a useful system to elucidate the mechanisms of intermediate mesoderm development and potentially providing a cell source for regenerative therapies of the kidney.

Kenji Osafune - One of the best experts on this subject based on the ideXlab platform.

  • efficient and rapid induction of human ipscs escs into nephrogenic intermediate mesoderm using small molecule based differentiation methods
    PLOS ONE, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

  • Efficient and rapid induction of human iPSCs/ESCs into nephrogenic intermediate mesoderm using small molecule-based differentiation methods.
    PloS one, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

Rudolf Winklbauer - One of the best experts on this subject based on the ideXlab platform.

  • EphrinB/EphB Signaling Controls Embryonic Germ Layer Separation by Contact-Induced Cell Detachment
    PLoS Biology, 2011
    Co-Authors: Nazanin Rohani, Laura Canty, Olivia Luu, François Fagotto, Rudolf Winklbauer
    Abstract:

    Background The primordial organization of the metazoan body is achieved during gastrulation by the establishment of the Germ Layers. Adhesion differences between ectoderm, mesoderm, and endoderm cells could in principle be sufficient to maintain Germ Layer integrity and prevent intermixing. However, in organisms as diverse as fly, fish, or amphibian, the ectoderm-mesoderm boundary not only keeps these Germ Layers separated, but the ectoderm also serves as substratum for mesoderm migration, and the boundary must be compatible with repeated cell attachment and detachment. Principal Findings We show that localized detachment resulting from contact-induced signals at the boundary is at the core of ectoderm-mesoderm segregation. Cells alternate between adhesion and detachment, and detachment requires ephrinB/EphB signaling. Multiple ephrinB ligands and EphB receptors are expressed on each side of the boundary, and tissue separation depends on forward signaling across the boundary in both directions, involving partially redundant ligands and receptors and activation of Rac and RhoA. Conclusion This mechanism differs from a simple differential adhesion process of Germ Layer formation. Instead, it involves localized responses to signals exchanged at the tissue boundary and an attachment/detachment cycle which allows for cell migration across a cellular substratum.

  • ephrinb ephb signaling controls Embryonic Germ Layer separation by contact induced cell detachment
    PLOS Biology, 2011
    Co-Authors: Nazanin Rohani, Laura Canty, Olivia Luu, François Fagotto, Rudolf Winklbauer
    Abstract:

    Background The primordial organization of the metazoan body is achieved during gastrulation by the establishment of the Germ Layers. Adhesion differences between ectoderm, mesoderm, and endoderm cells could in principle be sufficient to maintain Germ Layer integrity and prevent intermixing. However, in organisms as diverse as fly, fish, or amphibian, the ectoderm-mesoderm boundary not only keeps these Germ Layers separated, but the ectoderm also serves as substratum for mesoderm migration, and the boundary must be compatible with repeated cell attachment and detachment. Principal Findings We show that localized detachment resulting from contact-induced signals at the boundary is at the core of ectoderm-mesoderm segregation. Cells alternate between adhesion and detachment, and detachment requires ephrinB/EphB signaling. Multiple ephrinB ligands and EphB receptors are expressed on each side of the boundary, and tissue separation depends on forward signaling across the boundary in both directions, involving partially redundant ligands and receptors and activation of Rac and RhoA. Conclusion This mechanism differs from a simple differential adhesion process of Germ Layer formation. Instead, it involves localized responses to signals exchanged at the tissue boundary and an attachment/detachment cycle which allows for cell migration across a cellular substratum.

Toshikazu Araoka - One of the best experts on this subject based on the ideXlab platform.

  • efficient and rapid induction of human ipscs escs into nephrogenic intermediate mesoderm using small molecule based differentiation methods
    PLOS ONE, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

  • Efficient and rapid induction of human iPSCs/ESCs into nephrogenic intermediate mesoderm using small molecule-based differentiation methods.
    PloS one, 2014
    Co-Authors: Toshikazu Araoka, Shin Ichi Mae, Yuko Kurose, Motonari Uesugi, Akira Ohta, Shinya Yamanaka, Kenji Osafune
    Abstract:

    The first step in developing regenerative medicine approaches to treat renal diseases using pluripotent stem cells must be the generation of intermediate mesoderm (IM), an Embryonic Germ Layer that gives rise to kidneys. In order to achieve this goal, establishing an efficient, stable and low-cost method for differentiating IM cells using small molecules is required. In this study, we identified two retinoids, AM580 and TTNPB, as potent IM inducers by high-throughput chemical screening, and established rapid (five days) and efficient (80% induction rate) IM differentiation from human iPSCs using only two small molecules: a Wnt pathway activator, CHIR99021, combined with either AM580 or TTNPB. The resulting human IM cells showed the ability to differentiate into multiple cell types that constitute adult kidneys, and to form renal tubule-like structures. These small molecule differentiation methods can bypass the mesendoderm step, directly inducing IM cells by activating Wnt, retinoic acid (RA), and bone morphogenetic protein (BMP) pathways. Such methods are powerful tools for studying kidney development and may potentially provide cell sources to generate renal lineage cells for regenerative therapy.

Kazutoshi Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells
    Nature Communications, 2013
    Co-Authors: Shin Ichi Mae, Akemi Shono, Fumihiko Shiota, Tetsuhiko Yasuno, Masatoshi Kajiwara, Nanaka Gotodanishimura, Sayaka Arai, Aiko Satootubo, Taro Toyoda, Kazutoshi Takahashi
    Abstract:

    A method for stimulating the differentiation of human pluripotent stem cells into kidney lineages remains to be developed. Most cells in kidney are derived from an Embryonic Germ Layer known as intermediate mesoderm. Here we show the establishment of an efficient system of homologous recombination in human pluripotent stem cells by means of bacterial artificial chromosome-based vectors and single-nucleotide polymorphism array-based detection. This system allowed us to generate human-induced pluripotent stem cell lines containing green fluorescence protein knocked into OSR1, a specific intermediate mesoderm marker. We have also established a robust induction protocol for intermediate mesoderm, which produces up to 90% OSR1(+) cells. These human intermediate mesoderm cells can differentiate into multiple cell types of intermediate mesoderm-derived organs in vitro and in vivo, thereby supplying a useful system to elucidate the mechanisms of intermediate mesoderm development and potentially providing a cell source for regenerative therapies of the kidney.