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

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Title: Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs
Authors: Sone, Masamitsu Browse this author →KAKEN DB
Nakamura, Sou Browse this author
Umeda, Sachiko Browse this author
Ginya, Harumi Browse this author
Oshima, Motohiko Browse this author
Kanashiro, Maria Alejandra Browse this author
Paul, Sudip Kumar Browse this author
Hashimoto, Kanae Browse this author
Nakamura, Emiri Browse this author
Harada, Yasuo Browse this author
Tsujimura, Kyoko Browse this author
Saraya, Atsunori Browse this author
Yamaguchi, Tomoyuki Browse this author
Sugimoto, Naoshi Browse this author
Sawaguchi, Akira Browse this author
Iwama, Atsushi Browse this author
Eto, Koji Browse this author
Takayama, Naoya Browse this author
Issue Date: 14-Dec-2021
Publisher: Cell Press
Journal Title: Stem Cell Reports
Volume: 16
Issue: 12
Start Page: 2861
End Page: 2870
Publisher DOI: 10.1016/j.stemcr.2021.11.001
Abstract: 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.
Type: article
Appears in Collections:低温科学研究所 (Institute of Low Temperature Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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