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  1. Article: Recipe for pituitary organoids.

    Kano, Mayuko / Sasaki, Hiroo / Miwata, Tsutomu / Suga, Hidetaka

    Frontiers in endocrinology

    2023  Volume 13, Page(s) 1025825

    Abstract: Generation of a variety of organs and tissues from human pluripotent stem cells (hPSCs) has been ... ...

    Abstract Generation of a variety of organs and tissues from human pluripotent stem cells (hPSCs) has been attempted
    MeSH term(s) Animals ; Humans ; Mice ; Cell Differentiation ; Hedgehog Proteins ; Hypopituitarism ; Organoids ; Pituitary Gland
    Chemical Substances Hedgehog Proteins
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.1025825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Xenotransplantation and interspecies organogenesis: current status and issues.

    Kano, Mayuko / Mizutani, Eiji / Homma, Shota / Masaki, Hideki / Nakauchi, Hiromitsu

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 963282

    Abstract: Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, ... ...

    Abstract Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, transplantation of animal organs is expected to be an alternative method to solve the serious shortage of donor organs. More recently, a method to generate organs from pluripotent stem cells inside the body of other species has been developed. This interspecies organ generation using blastocyst complementation (BC) is expected to be the next-generation regenerative medicine. Here, we describe the recent advances and future prospects for these two approaches.
    MeSH term(s) Animals ; Blastocyst ; Organogenesis/physiology ; Pluripotent Stem Cells ; Regenerative Medicine ; Transplantation, Heterologous
    Language English
    Publishing date 2022-08-05
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.963282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine.

    Kano, Mayuko / Suga, Hidetaka / Arima, Hiroshi

    Journal of the Endocrine Society

    2020  Volume 5, Issue 3, Page(s) bvaa188

    Abstract: The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for ... ...

    Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.
    Language English
    Publishing date 2020-12-02
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2472-1972
    ISSN (online) 2472-1972
    DOI 10.1210/jendso/bvaa188
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  4. Article ; Online: Skin graft with dermis and appendages generated in vivo by cell competition.

    Nagano, Hisato / Mizuno, Naoaki / Sato, Hideyuki / Mizutani, Eiji / Yanagida, Ayaka / Kano, Mayuko / Kasai, Mariko / Yamamoto, Hiromi / Watanabe, Motoo / Suchy, Fabian / Masaki, Hideki / Nakauchi, Hiromitsu

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3366

    Abstract: Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although ... ...

    Abstract Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.
    MeSH term(s) Animals ; Skin Transplantation/methods ; Keratinocytes/cytology ; Keratinocytes/transplantation ; Humans ; Dermis/cytology ; Dermis/transplantation ; Mice, Knockout ; Mice ; Epidermis/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/transplantation ; Skin, Artificial ; Epidermal Cells/transplantation ; Epidermal Cells/cytology ; Extracellular Matrix/metabolism ; Skin/cytology
    Language English
    Publishing date 2024-04-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47527-7
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  5. Article: Association Between Caregiver's Perception of "Good" Dietary Habits and Food Group Intake Among Preschool Children in Tokyo, Japan.

    Kano, Mayuko / Tani, Yukako / Ochi, Manami / Sudo, Noriko / Fujiwara, Takeo

    Frontiers in pediatrics

    2020  Volume 7, Page(s) 554

    Abstract: Given that parents are mainly responsible for a preschooler's dietary management, they need to understand a child's diet. However, few studies have examined the association between parental perception of a preschool child's "good" dietary habits and ... ...

    Abstract Given that parents are mainly responsible for a preschooler's dietary management, they need to understand a child's diet. However, few studies have examined the association between parental perception of a preschool child's "good" dietary habits and actual food intake. We conducted a cross-sectional study investigating whether a child's food intake would differ depending on the caregiver's perception of their child's dietary habits among 4-year-old nursery school children at Adachi City, Tokyo, Japan. Children's dietary data were collected using the brief-type self-administered diet history questionnaire for children Aged 3-6 Years (BDHQ3y), while caregivers' perceptions of their child's dietary habits (good, normal, and poor) were inquired (
    Language English
    Publishing date 2020-01-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2019.00554
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Functional calcium-responsive parathyroid glands generated using single-step blastocyst complementation.

    Kano, Mayuko / Mizuno, Naoaki / Sato, Hideyuki / Kimura, Takaharu / Hirochika, Rei / Iwasaki, Yasumasa / Inoshita, Naoko / Nagano, Hisato / Kasai, Mariko / Yamamoto, Hiromi / Yamaguchi, Tomoyuki / Suga, Hidetaka / Masaki, Hideki / Mizutani, Eiji / Nakauchi, Hiromitsu

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 28, Page(s) e2216564120

    Abstract: Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better ... ...

    Abstract Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of
    MeSH term(s) Humans ; Animals ; Mice ; Rats ; Parathyroid Glands ; Calcium ; Hypoparathyroidism/genetics ; Hypoparathyroidism/therapy ; Calcium, Dietary ; Blastocyst
    Chemical Substances Calcium (SY7Q814VUP) ; Calcium, Dietary
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2216564120
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  7. Article ; Online: Functional Pituitary Tissue Generation from Human Embryonic Stem Cells.

    Kano, Mayuko / Suga, Hidetaka / Kasai, Takatoshi / Ozone, Chikafumi / Arima, Hiroshi

    Current protocols in neuroscience

    2018  Volume 83, Issue 1, Page(s) e48

    Abstract: The anterior pituitary gland produces several hormones essential for regulation of the somatic endocrine system. Deficiency of these hormones can cause life-threatening diseases, including adrenal crisis. Pituitary tissue generated from human pluripotent ...

    Abstract The anterior pituitary gland produces several hormones essential for regulation of the somatic endocrine system. Deficiency of these hormones can cause life-threatening diseases, including adrenal crisis. Pituitary tissue generated from human pluripotent stem cells is expected to provide better treatment than current hormone replacement therapy. During early mammalian development, the pituitary anlage (Rathke's pouch) develops from non-neural ectoderm adjacent to the developing ventral hypothalamus. The close interaction between these two tissues is crucial for Rathke's pouch development and involves several signaling molecules. Early exposure of human embryonic stem cells in 3D floating culture to sonic hedgehog and bone morphogenetic protein 4 promoted the cells' differentiation into oral ectoderm and, subsequently, hormone-producing cells such as corticotrophs (adrenocorticotropic hormone-producing cells). The differentiation approach described herein, which induces the formation of pituitary tissue in contact with hypothalamic neural tissue, mimics mammalian pituitary development. The differentiated corticotrophs are functional, responding normally to both release and feedback signals. © 2018 by John Wiley & Sons, Inc.
    MeSH term(s) Cell Culture Techniques/methods ; Cell Differentiation/physiology ; Embryonic Development/physiology ; Human Embryonic Stem Cells/pathology ; Humans ; Pituitary Gland/pathology ; Pluripotent Stem Cells/pathology
    Language English
    Publishing date 2018-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1934-8576
    ISSN (online) 1934-8576
    DOI 10.1002/cpns.48
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  8. Article ; Online: Investigation of Staphylococcus aureus positive for Staphylococcal enterotoxin S and T genes.

    Sato'o, Yusuke / Omoe, Katsuhiko / Aikawa, Yasuko / Kano, Mayuko / Ono, Hisaya K / Hu, Dong-Liang / Nakane, Akio / Sugai, Motoyuki

    The Journal of veterinary medical science

    2021  Volume 83, Issue 7, Page(s) 1120–1127

    Abstract: Staphylococcus aureus produces staphylococcal enterotoxins (SEs) and causes food poisoning. It is known that almost all SE-encoding genes are present on various types of mobile genetic elements and can mobilize among S. aureus populations. Further, ... ...

    Abstract Staphylococcus aureus produces staphylococcal enterotoxins (SEs) and causes food poisoning. It is known that almost all SE-encoding genes are present on various types of mobile genetic elements and can mobilize among S. aureus populations. Further, plasmids comprise one of SE gene carriers. Previously, we reported novel SEs, SES and SET, harbored by the plasmid pF5 from Fukuoka5. In the present study, we analyzed the distribution of these SEs in various S. aureus isolates in Japan. We used 526 S. aureus strains and found 311 strains positive for at least one SE/SE-like toxin gene, but only two strains (Fukuoka5 and Hiroshima3) were positive for ses and set among the specimens. We analyzed two plasmids (pF5 and pH3) from these strains and found that they were different. Whereas these plasmids partially shared similar sequences involved in the ser/selj/set/ses gene cluster, other sequences were different. A comparison of these plasmids with those deposited in the NCBI database revealed that only one plasmid had the ser/selj/set/ses cluster with a stop mutation in set similar to that in pH3. In addition, the chromosomes of Fukuoka5 and Hiroshima3, positive for ses and set, were classified into different genotypes. Despite the low rate of gene positivity for these SEs, it is suggested that there is diversity in plasmids and strains carrying these two SEs. Consequently, regarding the entire feature of SE prevalence, we improved the multiplex PCR detection method for the SE superfamily to obtain further insight.
    MeSH term(s) Animals ; Enterotoxins/genetics ; Food Microbiology ; Japan/epidemiology ; Staphylococcal Food Poisoning/veterinary ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/veterinary ; Staphylococcus aureus/genetics
    Chemical Substances Enterotoxins
    Language English
    Publishing date 2021-05-26
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1071753-5
    ISSN 1347-7439 ; 0916-7250
    ISSN (online) 1347-7439
    ISSN 0916-7250
    DOI 10.1292/jvms.20-0662
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  9. Article ; Online: Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells.

    Miwata, Tsutomu / Suga, Hidetaka / Kawaguchi, Yohei / Sakakibara, Mayu / Kano, Mayuko / Taga, Shiori / Soen, Mika / Ozaki, Hajime / Asano, Tomoyoshi / Sasaki, Hiroo / Miyata, Takashi / Yasuda, Yoshinori / Kobayashi, Tomoko / Sugiyama, Mariko / Onoue, Takeshi / Takagi, Hiroshi / Hagiwara, Daisuke / Iwama, Shintaro / Arima, Hiroshi

    Stem cell reports

    2023  Volume 18, Issue 4, Page(s) 869–883

    Abstract: When damaged, restoring the function of the hypothalamus is currently impossible. It is unclear whether neural stem cells exist in the hypothalamus. Studies have reported that adult rodent tanycytes around the third ventricle function as hypothalamic ... ...

    Abstract When damaged, restoring the function of the hypothalamus is currently impossible. It is unclear whether neural stem cells exist in the hypothalamus. Studies have reported that adult rodent tanycytes around the third ventricle function as hypothalamic neural stem cell-like cells. However, it is currently impossible to collect periventricular cells from humans. We attempted to generate hypothalamic neural stem cell-like cells from human embryonic stem cells (ESCs). We focused on retina and anterior neural fold homeobox (RAX) because its expression is gradually restricted to tanycytes during the late embryonic stage. We differentiated RAX::VENUS knockin human ESCs (hESCs) into hypothalamic organoids and sorted RAX
    MeSH term(s) Mice ; Animals ; Humans ; Neural Stem Cells ; Cell Differentiation/physiology ; Pluripotent Stem Cells ; Neurogenesis/physiology ; Hypothalamus/metabolism
    Language English
    Publishing date 2023-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2023.02.006
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  10. Article ; Online: Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state.

    Ozaki, Hajime / Suga, Hidetaka / Sakakibara, Mayu / Soen, Mika / Miyake, Natsuki / Miwata, Tsutomu / Taga, Shiori / Nagai, Takashi / Kano, Mayuko / Mitsumoto, Kazuki / Miyata, Takashi / Kobayashi, Tomoko / Sugiyama, Mariko / Onoue, Takeshi / Takagi, Hiroshi / Hagiwara, Daisuke / Iwama, Shintaro / Banno, Ryoichi / Iguchi, Genzo /
    Takahashi, Yutaka / Muguruma, Keiko / Inoue, Haruhisa / Arima, Hiroshi

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 17381

    Abstract: Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human ... ...

    Abstract Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) differentiate into AVP neurons, whereas human ESCs/iPSCs die. Human ESCs/iPSCs are generally more similar to mouse epiblast stem cells (mEpiSCs) compared to mouse ESCs. In this study, we converted human FNDI-specific iPSCs by the naive conversion kit. Although the conversion was partial, we found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.
    MeSH term(s) Animals ; Cell Differentiation ; Diabetes Insipidus, Neurogenic ; Humans ; Hypothalamus/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Neurons/metabolism ; Vasopressins/metabolism
    Chemical Substances Vasopressins (11000-17-2)
    Language English
    Publishing date 2022-10-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-22405-8
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