The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment

Andreas Brown, Johannes Pospiech, Karina Eiwen, Darren J Baker, Bettina Moehrle, Vadim Sakk, Kalpana Nattamai, Mona Vogel, Ani Grigoryan, Hartmut Geiger

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The spindle assembly checkpoint plays a pivotal role in preventing aneuploidy and transformation. Many studies demonstrate impairment of this checkpoint in cancer cells. While leukemia is frequently driven by transformed hematopoietic stem and progenitor cells (HSPCs), the biology of the spindle assembly checkpoint in such primary cells is not very well understood. Here, we reveal that the checkpoint is fully functional in murine progenitor cells and, to a lesser extent, in hematopoietic stem cells. We show that HSPCs arrest at prometaphase and induce p53-dependent apoptosis upon prolonged treatment with anti-mitotic drugs. Moreover, the checkpoint can be chemically and genetically abrogated, leading to premature exit from mitosis, subsequent enforced G1 arrest, and enhanced levels of chromosomal damage. We finally demonstrate that, upon checkpoint abrogation in HSPCs, hematopoiesis is impaired, manifested by loss of differentiation potential and engraftment ability, indicating a critical role of this checkpoint in HSPCs and hematopoiesis. In this report, Andreas Brown and colleagues demonstrate that cycling hematopoietic stem and progenitor cells activate the spindle assembly checkpoint as a response to anti-mitotic stress. The authors further reveal that inhibition of the checkpoint causes impairment of progenitor function, whereas it appears to be less crucial for hematopoietic stem cells.

Original languageEnglish (US)
Pages (from-to)1359-1368
Number of pages10
JournalStem Cell Reports
Volume9
Issue number5
DOIs
StatePublished - Nov 14 2017

Fingerprint

M Phase Cell Cycle Checkpoints
Hematopoietic Stem Cells
Stem cells
Cells
Apoptosis
Hematopoiesis
Pharmaceutical Preparations
Prometaphase
Aneuploidy
Mitosis
Cell Biology

Keywords

  • genome stability
  • hematopoiesis
  • hematopoietic progenitor cells
  • hematopoietic stem cells
  • micronuclei
  • mitotic checkpoint
  • reversine
  • SAC
  • spindle assembly checkpoint

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment. / Brown, Andreas; Pospiech, Johannes; Eiwen, Karina; Baker, Darren J; Moehrle, Bettina; Sakk, Vadim; Nattamai, Kalpana; Vogel, Mona; Grigoryan, Ani; Geiger, Hartmut.

In: Stem Cell Reports, Vol. 9, No. 5, 14.11.2017, p. 1359-1368.

Research output: Contribution to journalArticle

Brown, A, Pospiech, J, Eiwen, K, Baker, DJ, Moehrle, B, Sakk, V, Nattamai, K, Vogel, M, Grigoryan, A & Geiger, H 2017, 'The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment', Stem Cell Reports, vol. 9, no. 5, pp. 1359-1368. https://doi.org/10.1016/j.stemcr.2017.09.017
Brown, Andreas ; Pospiech, Johannes ; Eiwen, Karina ; Baker, Darren J ; Moehrle, Bettina ; Sakk, Vadim ; Nattamai, Kalpana ; Vogel, Mona ; Grigoryan, Ani ; Geiger, Hartmut. / The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment. In: Stem Cell Reports. 2017 ; Vol. 9, No. 5. pp. 1359-1368.
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