Assembly of a parts list of the human mitotic cell cycle machinery

Giotti, Bruno; Chen, Sz-Hau; Barnett, Mark W.; Regan, Tim; Ly, Tony; Wiemann, Stefan; Hume, David; Freeman, Tom C.

doi:10.1093/jmcb/mjy063

Cited by 69 publications

(82 citation statements)

References 74 publications

(118 reference statements)

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“…3g, h). Moreover, we did not find a global increase of S-and G2/Massociated transcripts (Giotti et al, 2018) in the P1P2dKO pro-B transcriptome (Fig. 4b).…”

Section: Ptbp1 Controls Cdk Activity In Pro-b Cellsmentioning

confidence: 66%

“…We only found one GO term amongst those enriched to be directly associated with proliferation: "cyclin-dependent protein serine/threonine kinase inhibitor activity". This was unexpected given the documented changes in the transcriptome across different phases of the cell cycle (Giotti et al, 2018) and that FrB pro-B cells from which we carried out mRNAseq in P1P2dKO mice have a ~10% increase of cells in S-phase and ~12% increase of cells in G2/M-phase compared to control and P1sKO FrB pro-B cells ( Supplementary Fig. 3g, h).…”

Section: Ptbp1 Controls Cdk Activity In Pro-b Cellsmentioning

confidence: 89%

“…Supplementary Table 6. DESeq2 results for genes shown to have high mRNA expression levels in S or G2M phases (Giotti et al, 2018) in the three pair-wise comparisons shown in Fig. 4b.…”

Section: Supplementary Tablementioning

confidence: 99%

“…Although our GO analysis of genes differentially expressed in P1P2dKO compared to control and P1sKO pro-B cells identified an enrichment for ribosome biogenesis and CDK inhibitors it did not identify further terms directly related with proliferation. We assessed changes in mRNA abundance of genes highly expressed specifically in the S and G2/Mphases of the cell cycle (Giotti et al, 2018) between FrB pro-B cells of the different genotypes. S-and G2/M-associated transcripts were not globally increased in P1P2dKO…”

Section: Ptbp1 Controls the Expression Of S-phase Entry Regulators Inmentioning

confidence: 99%

“…Results from gene ontology enrichment analysis carried out with the groups of genes identified in Figure 2D and Figure 2E. (Giotti et al, 2018) in the three pair-wise comparisons shown in Figure 6A.…”

Section: Supplemental Tablesmentioning

confidence: 99%

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Polypyrimidine Tract Binding Proteins are essential for B cell development

Monzón-Casanova

Matheson

Tabbada

et al. 2019

Preprint

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During B cell development, recombination of immunoglobulin loci is tightly coordinated with the cell cycle to avoid unwanted rearrangements of other genomic locations. Several factors have been identified that suppress proliferation in late-pre-B cells to allow light chain recombination. By comparison, our knowledge of factors limiting proliferation during heavy chain recombination at the pro-B cell stage is very limited. Here we identify an essential role for the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1) in B cell development. Absence of PTBP1 and the paralog PTBP2 results in a complete block in development at the pro-B cell stage. PTBP1 promotes the fidelity of the transcriptome in pro-B cells. In particular, PTBP1 controls a cell cycle mRNA regulon, suppresses entry into S-phase and promotes progression into mitosis. Our results highlight the importance of S-phase entry suppression and post-transcriptional gene expression control by PTBP1 in pro-B cells for proper B cell development.

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“…3g, h). Moreover, we did not find a global increase of S-and G2/Massociated transcripts (Giotti et al, 2018) in the P1P2dKO pro-B transcriptome (Fig. 4b).…”

Section: Ptbp1 Controls Cdk Activity In Pro-b Cellsmentioning

confidence: 66%

Section: Ptbp1 Controls Cdk Activity In Pro-b Cellsmentioning

confidence: 89%

“…Supplementary Table 6. DESeq2 results for genes shown to have high mRNA expression levels in S or G2M phases (Giotti et al, 2018) in the three pair-wise comparisons shown in Fig. 4b.…”

Section: Supplementary Tablementioning

confidence: 99%

Section: Ptbp1 Controls the Expression Of S-phase Entry Regulators Inmentioning

confidence: 99%

Section: Supplemental Tablesmentioning

confidence: 99%

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Polypyrimidine Tract Binding Proteins are essential for B cell development

Monzón-Casanova

Matheson

Tabbada

et al. 2019

Preprint

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WNT/beta-catenin signalling interrupts a senescence-induction cascade in human mesenchymal stem cells that restricts their expansion

Lehmann

Narcisi

Franceschini

et al. 2022

Cell. Mol. Life Sci.

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Senescence, the irreversible cell cycle arrest of damaged cells, is accompanied by a deleterious pro-inflammatory senescence-associated secretory phenotype (SASP). Senescence and the SASP are major factors in aging, cancer, and degenerative diseases, and interfere with the expansion of adult cells in vitro, yet little is known about how to counteract their induction and deleterious effects. Paracrine signals are increasingly recognized as important senescence triggers and understanding their regulation and mode of action may provide novel opportunities to reduce senescence-induced inflammation and improve cell-based therapies. Here, we show that the signalling protein WNT3A counteracts the induction of paracrine senescence in cultured human adult mesenchymal stem cells (MSCs). We find that entry into senescence in a small subpopulation of MSCs triggers a secretome that causes a feed-forward signalling cascade that with increasing speed induces healthy cells into senescence. WNT signals interrupt this cascade by repressing cytokines that mediate this induction of senescence. Inhibition of those mediators by interference with NF-κB or interleukin 6 signalling reduced paracrine senescence in absence of WNT3A and promoted the expansion of MSCs. Our work reveals how WNT signals can antagonize senescence and has relevance not only for expansion of adult cells but can also provide new insights into senescence-associated inflammatory and degenerative diseases.

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The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease

O’Brien,

Summers,

Martin

et al. 2024

Hum. Genet.

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The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.

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Assembly of a parts list of the human mitotic cell cycle machinery

Cited by 69 publications

References 74 publications

Polypyrimidine Tract Binding Proteins are essential for B cell development

Polypyrimidine Tract Binding Proteins are essential for B cell development

WNT/beta-catenin signalling interrupts a senescence-induction cascade in human mesenchymal stem cells that restricts their expansion

The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease

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