Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs.
Blood Platelets
/ metabolism
Cell Line
Cell Proliferation
Clone Cells
Cyclin-Dependent Kinase Inhibitor p21
/ metabolism
Gene Knockdown Techniques
Gene Silencing
HEK293 Cells
Humans
Induced Pluripotent Stem Cells
/ metabolism
Megakaryocyte Progenitor Cells
/ metabolism
Polycomb Repressive Complex 1
/ metabolism
Proto-Oncogene Proteins c-myc
/ metabolism
Tumor Suppressor Protein p53
/ metabolism
Up-Regulation
bcl-X Protein
/ metabolism
CDKN1A
cyclin-dependent kinase inhibitor
iPSC
immortalization
megakaryocyte
p53
platelet
regenerative medicine
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
14 12 2021
14 12 2021
Historique:
received:
01
10
2020
revised:
01
11
2021
accepted:
01
11
2021
pubmed:
4
12
2021
medline:
4
3
2022
entrez:
3
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34861163
pii: S2213-6711(21)00554-3
doi: 10.1016/j.stemcr.2021.11.001
pmc: PMC8693651
pii:
doi:
Substances chimiques
BMI1 protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
Proto-Oncogene Proteins c-myc
0
Tumor Suppressor Protein p53
0
bcl-X Protein
0
Polycomb Repressive Complex 1
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2861-2870Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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