Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics

Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda; Venugopal, Balaji; Marla, Vinay; Pillai, Malini S.; Kassem, Moustapha; Dhawan, Jyotsna

doi:10.1016/j.scr.2018.05.010

“…Induction of quiescence is associated with enhanced clonogenic self-renewal when cells are restored to proliferative conditions [16]. Cells with impaired ciliogenesis showed a deviation from canonical features of G0 such as expression of p27 and 2 N DNA content.…”

Section: Myoblasts Lacking Cilia Have Reduced Self-renewal Potentialmentioning

confidence: 99%

“…Previous studies [12][13][14][15] show that G0 can be distinguished from an extended G1 not only by the altered kinetics of entry into S phase, but by major alterations in the transcriptome. Indeed, analysis of G0 in multiple cell types points to the induction of a common cellular regenerative program in quiescence, suggesting a molecular basis for increased self-renewal [16]. The quiescent state is critical for the function of adult stem cells, which contribute to regeneration and tissue homeostasis (reviewed in [17]).…”

Section: Introductionmentioning

confidence: 99%

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

Venugopal

¹

,

Ghosh

²

,

Gala

³

et al. 2020

BMC Mol and Cell Biol

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Background: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. Results: Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. Conclusions: Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.

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“…Induction of quiescence is associated with enhanced clonogenic self-renewal when cells are restored to proliferative conditions (37). Cells with impaired ciliogenesis showed a deviation from canonical features of G0 such as expression of p27 and 2N DNA content.…”

Section: Myoblasts Lacking Cilia Have Reduced Self-renewal Potentialmentioning

confidence: 99%

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

Venugopal

¹

,

Ghosh

²

,

Gala

³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. Results Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro , but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. Conclusions Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.

show abstract

“…Induction of quiescence is associated with enhanced clonogenic self-renewal when cells are restored to proliferative conditions (38). Cells with impaired ciliogenesis showed a deviation from canonical features of G0 such as expression of p27 and 2N DNA content.…”

Section: Myoblasts Lacking Cilia Have Reduced Self-renewal Potentialmentioning

confidence: 99%

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

Venugopal

¹

,

Ghosh

²

,

Gala

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

Background Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. Results Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro , but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. Conclusions Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.

show abstract

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics

Cited by 32 publications

References 66 publications

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

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