2. Academic Validation
  3. Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2

Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2

  • Sci Rep. 2021 Dec 14;11(1):23977. doi: 10.1038/s41598-021-03298-5.
Kazuki Kumon 1,  Said M Afify 1 2,  Ghmkin Hassan 1 3,  Shunsuke Ueno 1,  Sadia Monzur 1,  Hend M Nawara 1,  Hagar A Abu Quora 1,  Mona Sheta 1,  Yanning Xu 4,  Xiaoying Fu 5,  Maram H Zahra 1,  Akimasa Seno 1,  Masaharu Seno 6
Affiliations

Affiliations

  • 1 Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan.
  • 2 Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufia University, Shebin El Koum, 32511, Egypt.
  • 3 Department of Microbiology and Biochemistry, Faculty of Pharmacy, Damascus University, Damascus, 10769, Syria.
  • 4 Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin, 300100, China.
  • 5 Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
  • 6 Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan. mseno@okayama-u.ac.jp.
PMID: 34907219 DOI: 10.1038/s41598-021-03298-5
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/Flt-1/2, 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/KDR/Flk-1 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.

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