TY - JOUR
T1 - Clonal hematopoiesis
T2 - mechanisms driving dominance of stem cell clones
AU - Challen, Grant A.
AU - Goodell, Margaret A.
N1 - Publisher Copyright:
© 2020 American Society of Hematology
PY - 2020/10/1
Y1 - 2020/10/1
N2 - The discovery of clonal hematopoiesis (CH) in older individuals has changed the way hematologists and stem cell biologists view aging. Somatic mutations accumulate in stem cells over time. While most mutations have no impact, some result in subtle functional differences that ultimately manifest in distinct stem cell behaviors. With a large pool of stem cells and many decades to compete, some of these differences confer advantages under specific contexts. Approximately 20 genes are recurrently found as mutated in CH, indicating they confer some advantage. The impact of these mutations has begun to be analyzed at a molecular level by modeling in cell lines and in mice. Mutations in epigenetic regulators such as DNMT3A and TET2 confer an advantage by enhancing self-renewal of stem and progenitor cells and inhibiting their differentiation. Mutations in other genes involved in the DNA damage response may simply enhance cell survival. Here, we review proposed mechanisms that lead to CH, specifically in the context of stem cell biology, based on our current understanding of the function of some of the CH-associated genes.
AB - The discovery of clonal hematopoiesis (CH) in older individuals has changed the way hematologists and stem cell biologists view aging. Somatic mutations accumulate in stem cells over time. While most mutations have no impact, some result in subtle functional differences that ultimately manifest in distinct stem cell behaviors. With a large pool of stem cells and many decades to compete, some of these differences confer advantages under specific contexts. Approximately 20 genes are recurrently found as mutated in CH, indicating they confer some advantage. The impact of these mutations has begun to be analyzed at a molecular level by modeling in cell lines and in mice. Mutations in epigenetic regulators such as DNMT3A and TET2 confer an advantage by enhancing self-renewal of stem and progenitor cells and inhibiting their differentiation. Mutations in other genes involved in the DNA damage response may simply enhance cell survival. Here, we review proposed mechanisms that lead to CH, specifically in the context of stem cell biology, based on our current understanding of the function of some of the CH-associated genes.
UR - http://www.scopus.com/inward/record.url?scp=85092682353&partnerID=8YFLogxK
U2 - 10.1182/blood.2020006510
DO - 10.1182/blood.2020006510
M3 - Review article
C2 - 32746453
AN - SCOPUS:85092682353
SN - 0006-4971
VL - 136
SP - 1590
EP - 1598
JO - Blood
JF - Blood
IS - 14
ER -