Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state
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 ch...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22405-8 |
| _version_ | 1811336516044062720 |
|---|---|
| author | Hajime Ozaki Hidetaka Suga Mayu Sakakibara Mika Soen Natsuki Miyake Tsutomu Miwata Shiori Taga Takashi Nagai Mayuko Kano Kazuki Mitsumoto Takashi Miyata Tomoko Kobayashi Mariko Sugiyama Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Shintaro Iwama Ryoichi Banno Genzo Iguchi Yutaka Takahashi Keiko Muguruma Haruhisa Inoue Hiroshi Arima |
| author_facet | Hajime Ozaki Hidetaka Suga Mayu Sakakibara Mika Soen Natsuki Miyake Tsutomu Miwata Shiori Taga Takashi Nagai Mayuko Kano Kazuki Mitsumoto Takashi Miyata Tomoko Kobayashi Mariko Sugiyama Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Shintaro Iwama Ryoichi Banno Genzo Iguchi Yutaka Takahashi Keiko Muguruma Haruhisa Inoue Hiroshi Arima |
| author_sort | Hajime Ozaki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:40:42Z |
| format | Article |
| id | doaj.art-94c212da469e43d0977e7e82b9d91bcb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:40:42Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-94c212da469e43d0977e7e82b9d91bcb2022-12-22T02:37:11ZengNature PortfolioScientific Reports2045-23222022-10-0112111110.1038/s41598-022-22405-8Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive stateHajime Ozaki0Hidetaka Suga1Mayu Sakakibara2Mika Soen3Natsuki Miyake4Tsutomu Miwata5Shiori Taga6Takashi Nagai7Mayuko Kano8Kazuki Mitsumoto9Takashi Miyata10Tomoko Kobayashi11Mariko Sugiyama12Takeshi Onoue13Hiroshi Takagi14Daisuke Hagiwara15Shintaro Iwama16Ryoichi Banno17Genzo Iguchi18Yutaka Takahashi19Keiko Muguruma20Haruhisa Inoue21Hiroshi Arima22Department of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineDivision of Diabetes and Endocrinology, Kobe University HospitalDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of MedicineRIKEN Center for Developmental Biology (CDB)Center for iPS Cell Research and Application (CiRA), Kyoto UniversityDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-022-22405-8 |
| spellingShingle | Hajime Ozaki Hidetaka Suga Mayu Sakakibara Mika Soen Natsuki Miyake Tsutomu Miwata Shiori Taga Takashi Nagai Mayuko Kano Kazuki Mitsumoto Takashi Miyata Tomoko Kobayashi Mariko Sugiyama Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Shintaro Iwama Ryoichi Banno Genzo Iguchi Yutaka Takahashi Keiko Muguruma Haruhisa Inoue Hiroshi Arima Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state Scientific Reports |
| title | Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| title_full | Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| title_fullStr | Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| title_full_unstemmed | Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| title_short | Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| title_sort | differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state |
| url | https://doi.org/10.1038/s41598-022-22405-8 |
| work_keys_str_mv | AT hajimeozaki differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT hidetakasuga differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT mayusakakibara differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT mikasoen differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT natsukimiyake differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT tsutomumiwata differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT shioritaga differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT takashinagai differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT mayukokano differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT kazukimitsumoto differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT takashimiyata differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT tomokokobayashi differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT marikosugiyama differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT takeshionoue differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT hiroshitakagi differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT daisukehagiwara differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT shintaroiwama differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT ryoichibanno differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT genzoiguchi differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT yutakatakahashi differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT keikomuguruma differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT haruhisainoue differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate AT hiroshiarima differentiationofhumaninducedpluripotentstemcellsintohypothalamicvasopressinneuronswithminimalexogenoussignalsandpartialconversiontothenaivestate |