The role of telomere binding molecules for normal and abnormal hematopoiesis

研究成果: ジャーナルへの寄稿評論記事

3 引用 (Scopus)

抄録

In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.

元の言語英語
ページ(範囲)646-655
ページ数10
ジャーナルInternational journal of hematology
107
発行部数6
DOI
出版物ステータス出版済み - 6 1 2018

Fingerprint

Telomere
Hematopoiesis
Hematopoietic Stem Cells
Hematopoietic System
DNA Damage
Dyskeratosis Congenita
Maintenance
Phenotype
Cell Division
Homeostasis
Theoretical Models
Genome

All Science Journal Classification (ASJC) codes

  • Hematology

これを引用

The role of telomere binding molecules for normal and abnormal hematopoiesis. / Hosokawa, Kentaro; Arai, Fumio.

:: International journal of hematology, 巻 107, 番号 6, 01.06.2018, p. 646-655.

研究成果: ジャーナルへの寄稿評論記事

@article{705f37a3bcdf4ceaa4784383b0b1a5d2,
title = "The role of telomere binding molecules for normal and abnormal hematopoiesis",
abstract = "In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.",
author = "Kentaro Hosokawa and Fumio Arai",
year = "2018",
month = "6",
day = "1",
doi = "10.1007/s12185-018-2432-4",
language = "English",
volume = "107",
pages = "646--655",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "6",

}

TY - JOUR

T1 - The role of telomere binding molecules for normal and abnormal hematopoiesis

AU - Hosokawa, Kentaro

AU - Arai, Fumio

PY - 2018/6/1

Y1 - 2018/6/1

N2 - In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.

AB - In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.

UR - http://www.scopus.com/inward/record.url?scp=85044067636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044067636&partnerID=8YFLogxK

U2 - 10.1007/s12185-018-2432-4

DO - 10.1007/s12185-018-2432-4

M3 - Review article

C2 - 29550946

AN - SCOPUS:85044067636

VL - 107

SP - 646

EP - 655

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

IS - 6

ER -