リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs

Sone, Masamitsu Nakamura, Sou Umeda, Sachiko Ginya, Harumi Oshima, Motohiko Kanashiro, Maria Alejandra Paul, Sudip Kumar Hashimoto, Kanae Nakamura, Emiri Harada, Yasuo Tsujimura, Kyoko Saraya, Atsunori Yamaguchi, Tomoyuki Sugimoto, Naoshi Sawaguchi, Akira Iwama, Atsushi Eto, Koji Takayama, Naoya 京都大学 DOI:10.1016/j.stemcr.2021.11.001

2021.12

概要

Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential of universal HLA-null platelet products have stimulated research on the ex vivo differentiation of human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, and BCL-XL (MBX). imMKCLs can act as cryopreservable master cells to supply platelet concentrates. However, the proliferation rates of the imMKCLs vary with the starting hPSC clone. In this study, we reveal from the gene expression profiles of several MKCL clones that the proliferation arrest is correlated with the expression levels of specific cyclin-dependent kinase inhibitors. Silencing CDKN1A and p53 with the overexpression of MBX was effective at stably inducing imMKCLs that generate functional platelets irrespective of the hPSC clone. Collectively, this improvement in generating imMKCLs should contribute to platelet industrialization and platelet biology.

この論文で使われている画像

関連論文

参考文献

Brummelkamp, T.R., Bernards, R., and Agami, R. (2002). A system for stable expression of short interfering RNAs in mammalian cells.

Science 296, 550-553.

Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J.P., Sedivy, J.M., Kinzler, K.W., and Vogelstein, B. (1998). Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282, 1497-1501.

Ho-Tin-Noe, B., Boulaftali, Y., and Camerer, E. (2018). Platelets and vascular integrity: how platelets prevent bleeding in inflamma-tion. Blood 131, 277-288.

Ito, Y., Nakamura, S., Sugimoto, N., Shigemori, I., Kato, Y., Ohno,

M., Sakuma, s., Ito, K., Kumon, H., Hirose, H., et al. (2018). Turbu-

lence activates platelet biogenesis to enable clinical scale ex vivo production. Cell 174, 636-648.18.

Kim, E.M., Jung, C.-H., Kim, J., Hwang, S.-G., Park, J.K., and Um, H.-D. (2017). The p53/p21 complex regulates cancer cell invasion and apoptosis by targeting Bcl-2 family proteins. Cancer Res. 77, 3092-3100.

Kim, J., Bae, s., An, S., Park, J.K., Kim, E.M., Hwang, s., Kim, W., and Um, H. (2014). Cooperative actions of p21 WAF 1 and p53 induce slug protein degradation and suppress cell invasion. EMBO Rep.

15, 1062-1068.

Löhr, K., Möritz, C., Contente, A., and Dobbelstein, M. (2003). p21/CDKN1A mediates negative regulation of transcription by p53. J. Biol. Chem. 278, 32507-32516.

Millau, J.-F., Wijchers, P., and Gaudreau, L. (2016). High-resolution

4C reveals rapid p53-dependent chromatin reorganization of the

CDKN1A locus in response to stress. PLoS One 11, e0163885.

Mohapatra, P., Preet, R., Das, D., Satapathy, S.R., Choudhuri, T., Wyatt, M.D., and Kundu, C.N. (2012). Quinacrine-mediated auto-phagy and apoptosis in colon cancer cells is through a p53- and p21-dependent mechanism. Oncol. Res. 20, 81-91.

Nakamura, S., Takayama, N., Hirata, S., Seo, H., Endo, H., Ochi, K., Fujita, K., Koike, T., Harimoto, K., Dohda, T., et al. (2014). Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells. Cell Stem Cell 14, 535-548.

Suzuki, D., Flahou, C., Yoshikawa, N., Stirblyte, 1., Hayashi, Y., Sa-waguchi, A., Akasaka, M., Nakamura, S., Higashi, N., Xu, H., et al.

(2020). iPSC-derived platelets depleted of HLA class I are inert to anti-HLA class I and natural killer cell immunity. Stem Cell Reports

14, 49-59.

Takayama, N., and Eto, K. (2012). In vitro generation of megakar-yocytes and platelets from human embryonic stem cells and induced pluripotent stem cells. Methods Mol. Biol. 788, 205-217.

Takayama, N., Nishikii, H., Usui, J., Tsukui, H., Sawaguchi, A., Hiroyama, T., Eto, K., and Nakauchi, H. (2008). Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hemato-poetic progenitors. Blood 111, 5298-5306.

Takayama, N., Nishimura, S., Nakamura, S., Shimizu, T., Ohnishi,

R., Endo, H., Yamaguchi, T., Otsu, M., Nishimura, K., Nakanishi,

M., et al. (2010). Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells. J. Exp. Med. 207, 2817-2830.

Voorhoeve, P.M., and Agami, R. (2003). The tumor-suppressive functions of the human INK4A locus. Cancer Cell 4, 311-319.

Zhang, Y., Yan, W., Jung, Y.S., and Chen, X. (2013). PUMA cooperates with p21 to regulate mammary epithelial morphogenesis and epithelial-to-mesenchymal transition. PLoS One 8, e66464.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る