Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Matsumoto, Ryusaku; Suga, Hidetaka; Aoi, Takashi; Bando, Hironori; Fukuoka, Hidenori; Iguchi, Genzo; Narumi, Shunji; Hasegawa, Tomonobu; Muguruma, Keiko; Ogawa, Wataru; Takahashi, Yutaka

doi:10.1172/jci127378

Cited by 55 publications

(39 citation statements)

References 56 publications

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“…They showed that the patient derived iPSCs were incapable of differentiating into hormone producing cells in contrast to control iPSCs. However, correcting this mutation by CRISPR/Cas-9 methodology modified the capacity of the iPSCs to fully differentiate into pituitary hormonal cells, validating that this variant was the one causing the hormone deficiency ( 52 ).…”

Section: Pituitary Stem Cells In Regenerative Medicinementioning

confidence: 99%

From Pituitary Stem Cell Differentiation to Regenerative Medicine

et al. 2021

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The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise during embryonic development, from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. Human and mouse embryonic stem cells can differentiate into all major hormone-producing cell types of the anterior lobe in a highly plastic and dynamic manner. More recently human induced pluripotent stem cells (iPSCs) emerged as a viable alternative due to their plasticity and high proliferative capacity. This mini-review gives an overview of the major advances that have been achieved to develop protocols to generate pituitary hormone-producing cell types from stem cells and how these mechanisms are regulated. We also discuss their application in pituitary diseases, such as pituitary hormone deficiencies.

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Section: Pituitary Stem Cells In Regenerative Medicinementioning

confidence: 99%

From Pituitary Stem Cell Differentiation to Regenerative Medicine

et al. 2021

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“…Otx2 auto-regulation appears to be via the CRM E in early chick retina, as we report here, and via Otx2 CRM 05 in mouse BP cells, as we found recently 40 , with these two CRMs sharing highly conserved sequences. Otx2 auto-regulation may be a theme for this gene, as it has been proposed in other contexts as well 79,80 . Otx2 auto-regulation, as well as its direct binding to cone genes, might suggest that Otx2 is a terminal selector gene 81 for photoreceptors.…”

Section: Discussionmentioning

confidence: 64%

Otx2 and Oc1 directly regulate the transcriptional program of cone photoreceptor development

Lonfat

Wang

Lee

et al. 2020

Preprint

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AbstractThe vertebrate retina is a highly organized structure of approximately 110 cell types. Retinal progenitor cells (RPCs) produce these cell types in a temporal order that is highly conserved. While some RPCs produce many cell types, some terminally dividing RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). Here, we compared the transcriptomes and chromatin profiles of such a restricted cone/HC RPC with those of other RPCs. We identified many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. We then showed that Otx2 and Oc1 directly regulate the activity of multiple CRMs genome-wide, including near genes important for cone development, such as Rxrg and Neurod1. In addition, we found that Otx2 regulates itself. These results suggest that Otx2 and Oc1 have a broader role than previously appreciated, and deepen our understanding of retinal development, which may benefit therapies for retinal diseases.

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“…We recently established an iPSC‐based congenital pituitary hypoplasia model (Matsumoto et al., 2019). These were disease‐specific iPS cells from a patient with panhypopituitarism who had a heterozygous mutation in OTX2, which determined the development of the forebrain, eye, and pituitary.…”

Section: Future Perspectivesmentioning

confidence: 99%

Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

2021

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The hypothalamic-pituitary system is essential for maintaining physiological homeostasis by controlling systemic hormones, but its regeneration remains mostly unclear. Therefore, attention is focused on the regeneration of the hypothalamus and pituitary from stem cells. Somatic stem cells have drawn attention for their potential for use in regenerative medicine. In the adenohypophysis, the existence of somatic stem cells was reported (Chen et al., 2005), and their functions were discussed at three phases: during early postnatal pituitary maturation (

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Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Cited by 55 publications

References 56 publications

From Pituitary Stem Cell Differentiation to Regenerative Medicine

From Pituitary Stem Cell Differentiation to Regenerative Medicine

Otx2 and Oc1 directly regulate the transcriptional program of cone photoreceptor development

Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

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