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

p53 Blood Platelets Cyclin-Dependent Kinase Inhibitor p21 Induced Pluripotent Stem Cells bcl-X Protein regenerative medicine immortalization Cell Line megakaryocyte Proto-Oncogene Proteins c-myc 03 medical and health sciences Report Humans Gene Silencing Cell Proliferation Megakaryocyte Progenitor Cells platelet Polycomb Repressive Complex 1 460 0303 health sciences iPSC cyclin-dependent kinase inhibitor Clone Cells Up-Regulation CDKN1A HEK293 Cells Gene Knockdown Techniques Tumor Suppressor Protein p53
DOI: 10.1016/j.stemcr.2021.11.001 Publication Date: 2021-12-02T15:30:19Z
ABSTRACT
Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential universal HLA-null platelet products have stimulated research ex vivo differentiation human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, BCL-XL (MBX). imMKCLs can act as cryopreservable master supply concentrates. However, proliferation rates vary with starting hPSC clone. In this study, we reveal gene expression profiles several MKCL clones that arrest is correlated levels specific cyclin-dependent kinase inhibitors. Silencing CDKN1A p53 overexpression MBX was effective at stably inducing generate functional platelets irrespective Collectively, improvement in generating should contribute industrialization biology.
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