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Effects of signaling pathway inhibitors on hematopoietic stem cells

  • Authors:
    • Yuyu Jiang
    • Zhaofeng Xu
    • Na Ma
    • Lizhi Yin
    • Caiqin Hao
    • Jing Li
  • View Affiliations / Copyright

    Affiliations: Stem Cell Laboratory, Department of Biology, College of Life Sciences, Shanghai Normal University, Shanghai 200234, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 9
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    Published online on: November 3, 2020
       https://doi.org/10.3892/mmr.2020.11647
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Abstract

While there are numerous small molecule inhibitory drugs available for a wide range of signalling pathways, at present, they are generally not used in combination in clinical settings. Previous reports have reported that the effects of glycogen synthase kinase (GSK)3β, p38MAPK, mTOR and histone deacetylase signaling combined together to suppress the stem‑like nature of hematopoietic stem cells (HSCs), driving these cells to differentiate, cease proliferating and thereby impairing normal hematopoietic functionality. The present study aimed to determine the effect of HDACs, mTOR, GSK‑3β and p38MAPK inhibitor combinations on the efficient expansion of HSCs using flow cytometry. Moreover, it specifically aimed to determine how inhibitors of the GSK3β signaling pathway, in combination with inhibitors of P38MAPK and mTOR signaling or histone deacetylase (HDAC) inhibitors, could affect HSC expansion, with the goal of identifying novel combination strategies useful for the expansion of HSCs. The results indicated that p38MAPK and/or GSK3β inhibitors increased Lin‑ cell and Lin‑Sca‑1+c‑kit+ (LSK) cell numbers in vitro. Taken together, these results suggested that a combination of p38MAPK and GSK3β signaling may regulate HSC differentiation in vitro. These findings further indicated that the suppression of p38MAPK and/or GSK3β signalling may modulate HSC differentiation and self‑renewal to enhance HSC expansion.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang Y, Xu Z, Ma N, Yin L, Hao C and Li J: Effects of signaling pathway inhibitors on hematopoietic stem cells. Mol Med Rep 23: 9, 2021.
APA
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., & Li, J. (2021). Effects of signaling pathway inhibitors on hematopoietic stem cells. Molecular Medicine Reports, 23, 9. https://doi.org/10.3892/mmr.2020.11647
MLA
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., Li, J."Effects of signaling pathway inhibitors on hematopoietic stem cells". Molecular Medicine Reports 23.1 (2021): 9.
Chicago
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., Li, J."Effects of signaling pathway inhibitors on hematopoietic stem cells". Molecular Medicine Reports 23, no. 1 (2021): 9. https://doi.org/10.3892/mmr.2020.11647
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang Y, Xu Z, Ma N, Yin L, Hao C and Li J: Effects of signaling pathway inhibitors on hematopoietic stem cells. Mol Med Rep 23: 9, 2021.
APA
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., & Li, J. (2021). Effects of signaling pathway inhibitors on hematopoietic stem cells. Molecular Medicine Reports, 23, 9. https://doi.org/10.3892/mmr.2020.11647
MLA
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., Li, J."Effects of signaling pathway inhibitors on hematopoietic stem cells". Molecular Medicine Reports 23.1 (2021): 9.
Chicago
Jiang, Y., Xu, Z., Ma, N., Yin, L., Hao, C., Li, J."Effects of signaling pathway inhibitors on hematopoietic stem cells". Molecular Medicine Reports 23, no. 1 (2021): 9. https://doi.org/10.3892/mmr.2020.11647
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