TY - JOUR
T1 - Normal hematopoiesis is a balancing act of self-renewal and regeneration
AU - Olson, Oakley C.
AU - Kang, Yoon A.
AU - Passegué, Emmanuelle
N1 - Funding Information:
O.C.O. is supported by National Institutes of Health (NIH) T32HL120826, and Y.-A.K. by a Leukemia & Lymphoma Society (LLS) Special Fellowship. This work was supported by NIH grant 1R35HL135763 to E.P. The authors have no conflicts of interest to disclose.
Publisher Copyright:
© 2020 Cold Spring Harbor Laboratory Press; all rights reserved;.
PY - 2020/12
Y1 - 2020/12
N2 - The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory cytokines and regenerative challenges. This activation phase leads to many intrinsic stresses such as replicative, meta-bolic, and oxidative stress, which can cause functional decline, impaired self-renewal, and exhaustion of HSCs. To cope with these insults, HSCs use both built-in and emergency-trig-gered stress-response mechanisms to maintain homeostasis and to defend against disease development. In this review, we discuss how the hematopoietic system operates in steady state and stress conditions, what strategies are used to maintain functional integrity, and how deregulation in the balance between self-renewal and regeneration can drive malignant trans-formation.
AB - The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory cytokines and regenerative challenges. This activation phase leads to many intrinsic stresses such as replicative, meta-bolic, and oxidative stress, which can cause functional decline, impaired self-renewal, and exhaustion of HSCs. To cope with these insults, HSCs use both built-in and emergency-trig-gered stress-response mechanisms to maintain homeostasis and to defend against disease development. In this review, we discuss how the hematopoietic system operates in steady state and stress conditions, what strategies are used to maintain functional integrity, and how deregulation in the balance between self-renewal and regeneration can drive malignant trans-formation.
UR - http://www.scopus.com/inward/record.url?scp=85091280948&partnerID=8YFLogxK
U2 - 10.1101/cshperspect.a035519
DO - 10.1101/cshperspect.a035519
M3 - Article
C2 - 31988205
AN - SCOPUS:85091280948
SN - 2157-1422
VL - 10
SP - 1
EP - 23
JO - Cold Spring Harbor perspectives in medicine
JF - Cold Spring Harbor perspectives in medicine
IS - 12
M1 - a035519
ER -