RRC ID 69008
Author Kumon K, Afify SM, Hassan G, Ueno S, Monzur S, Nawara HM, Quora HAA, Sheta M, Xu Y, Fu X, Zahra MH, Seno A, Seno M.
Title Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2.
Journal Sci Rep
Abstract Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34+ and c-kit+ was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.
Volume 11(1)
Pages 23977
Published 2021-12-14
DOI 10.1038/s41598-021-03298-5
PII 10.1038/s41598-021-03298-5
PMID 34907219
PMC PMC8671479
MeSH Animals Antigens, Differentiation / biosynthesis* Cell Differentiation / drug effects* Cell Hypoxia / drug effects Cobalt / pharmacology* Erythroblasts / metabolism* Gene Expression Regulation / drug effects* Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells / metabolism*
IF 3.998
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001)