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
AUTHORS (18)
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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CITATIONS (11)
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