The role of telomere binding molecules for normal and abnormal hematopoiesis

Hosokawa, Kentaro; Arai, Fumio

doi:10.1007/s12185-018-2432-4

Cited by 9 publications

(10 citation statements)

References 96 publications

(119 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most HSCs are in quiescent state under homeostasis, and cycle infrequently for self-renewal or to differentiate into multipotent progenitors (MPPs) and more committed progenitors, with limited self-renewal potential. Hematopoiesis is carefully regulated by both extrinsic and intrinsic mechanism(s), which balance quiescence, self-renewal and differentiation to support normal multi-lineage reconstitution [1][2][3]. In 1978, Ray Schofield first introduced the important regulatory role of bone marrow niche for HSCs.…”

Section: Introductionmentioning

confidence: 99%

Role of microvascular endothelial cells on proliferation, migration and adhesion of hematopoietic stem cells

et al. 2020

View full text Add to dashboard Cite

Background: The present study investigated the effects of microvascular endothelial cells (MECs) on the chemotaxis, adhesion and proliferation of bone marrow hematopoietic stem cells (HSCs) ex vivo. Methods and Results: MECs were collected from the lung tissue of C57BL/6 mice, and HSCs were isolated with immunomagnetic beads from bone marrow of GFP mice. MECs and HSCs were co-cultured with or without having direct cell–cell contact in Transwell device for the measurement of chemotaxis and adhesion of MECs to HSCs. Experimental results indicate that the penetration rate of HSCs from the Transwell upper chamber to lower chamber in ‘co-culture’ group was significantly higher than that of ‘HSC single culture’ group. Also, the HSCs in co-culture group were all adherent at 24 h, and the co-culture group with direct cell–cell contact had highest proliferation rate. The HSC number was positively correlated with vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) levels in supernatants of the culture. Conclusions: Our study reports that MECs enhance the chemotaxis, adhesion and proliferation of HSCs, which might be related to cytokines SDF-1 and VEGF secreted by MECs, and thus MECs enhance the HSC proliferation through cell–cell contact. The present study revealed the effect of MECs on HSCs, and provided a basis and direction for effective expansion of HSCs ex vivo.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of microvascular endothelial cells on proliferation, migration and adhesion of hematopoietic stem cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Recently, several reports highlighted the importance of shelterin complex in hematopoiesis, DC and CP [8,118]. DC is characterized by a disordered human telomere with many pleiotropic manifestations that often lead to the BM failure [119,120].…”

Section: Role Of Shelterin Complex In DC and Cpmentioning

confidence: 99%

Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations

Amir

Khan

Queen

et al. 2020

Cells

View full text Add to dashboard Cite

Telomere comprises the ends of eukaryotic linear chromosomes and is composed of G-rich (TTAGGG) tandem repeats which play an important role in maintaining genome stability, premature aging and onsets of many diseases. Majority of the telomere are replicated by conventional DNA replication, and only the last bit of the lagging strand is synthesized by telomerase (a reverse transcriptase). In addition to replication, telomere maintenance is principally carried out by two key complexes known as shelterin (TRF1, TRF2, TIN2, RAP1, POT1, and TPP1) and CST (CDC13/CTC1, STN1, and TEN1). Shelterin protects the telomere from DNA damage response (DDR) and regulates telomere length by telomerase; while, CST govern the extension of telomere by telomerase and C strand fill-in synthesis. We have investigated both structural and biochemical features of shelterin and CST complexes to get a clear understanding of their importance in the telomere maintenance. Further, we have analyzed ~115 clinically important mutations in both of the complexes. Association of such mutations with specific cellular fault unveils the importance of shelterin and CST complexes in the maintenance of genome stability. A possibility of targeting shelterin and CST by small molecule inhibitors is further investigated towards the therapeutic management of associated diseases. Overall, this review provides a possible direction to understand the mechanisms of telomere borne diseases, and their therapeutic intervention.

show abstract

mentioning

confidence: 99%

“…Telomere binding complexes, such as shelterin, are known to protect telomeres from DNA repair mechanisms, as well as to regulate telomerase activity (23,24). Six protein subunits (TRF1, TRF2, RAP1, TIN2, TPP1, and POT1) that form the shelterin complex are supposed to be involved in this activity (24). TRF1 in co-action with both Tankyrase 1 (TNKS1/ARTD5/PARP5a) and Tankyrase 2 (TNKS2/ARTD6/ PARP5b) controls telomere length negatively (telomere shortening is a result of TRF1 overexpression, while telomere lengthening is due to dominant-negative TRF1) (25,26).…”

mentioning

confidence: 99%

Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma

Vaičiulis

Liutkevičienė

Liutkevičius

et al. 2020

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: The study aimed to evaluate associations of relative leukocyte telomere length (LTL) and polymorphisms of telomere length-associated genes TERT (rs2736098), TERT-CLPTM1L (rs401681), TRF1 (rs1545827, rs10107605) and TNKS2 (rs10509637, rs10509639) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and Methods: The study consisted of 300 patients with LSCC and 369 healthy control subjects. Genotyping and relative LTL measuring were carried out using qPCR. Results: Relative LTL was statistically significantly shorter in the G3 (tumor differentiation grade) subgroup of patients with LSCC compared to the G1 and G2 subgroups. Significant differences were found in genotype distributions of TERT rs401681 and TNKS2 rs10509639 between the study groups. TERT rs401681 C/T and T/T genotypes were associated with approximately 30% decreased odds of LSCC development. Conclusion: LTL was shorter in the G3 subgroup compared to the G2 and G1 subgroups of LSCC patients. TERT rs401681 and its C/T and T/T genotypes were associated with decreased odds of overall LSCC development. Laryngeal squamous cell carcinoma (LSCC) represents one of the most common upper respiratory tract tumors and ranks 20th among all oncological diseases in Europe (1). According to published data, LSCC accounts for 2.4% of all 431 This article is freely accessible online.

show abstract

The role of telomere binding molecules for normal and abnormal hematopoiesis

Cited by 9 publications

References 96 publications

Role of microvascular endothelial cells on proliferation, migration and adhesion of hematopoietic stem cells

Role of microvascular endothelial cells on proliferation, migration and adhesion of hematopoietic stem cells

Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations

Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma

Contact Info

Product

Resources

About