TY - JOUR
T1 - Fitness selection in human pluripotent stem cells and interspecies chimeras
T2 - Implications for human development and regenerative medicine
AU - Wu, Jun
AU - Barbaric, Ivana
N1 - Funding Information:
The work in IB laboratory is supported by the grant from the UK Regenerative Medicine Platform , MRC reference MR/R015724/1 . J.W. is a Virginia Murchison Linthicum Scholar in Medical Research and funded by Cancer Prevention & Research Institute of Texas (CPRIT # RR170076 ) and Hamon Center for Regenerative Science & Medicine .
Publisher Copyright:
© 2021
PY - 2021/8
Y1 - 2021/8
N2 - A small number of pluripotent cells within early embryo gives rise to all cells in the adult body, including germ cells. Hence, any mutations occurring in the pluripotent cell population are at risk of being propagated to their daughter cells and could lead to congenital defects or embryonic lethality and pose a risk of being transmitted to future generations. The observation that genetic errors are relatively common in preimplantation embryos, but their levels reduce as development progresses, suggests the existence of mechanisms for clearance of aberrant, unfit or damaged cells. Although early human embryogenesis is largely experimentally inaccessible, pluripotent stem cell (PSC) lines can be derived either from the inner cell mass (ICM) of a blastocyst or by reprogramming somatic cells into an embryonic stem cell-like state. PSCs retain the ability to differentiate into any cell type in vitro and, hence, they represent a unique and powerful tool for studying otherwise intractable stages of human development. The advent of PSCs has also opened up a possibility of developing regenerative medicine therapies, either through PSC differentiation in vitro or by creating interspecies chimeras for organ replacement. Here, we discuss the emerging evidence of cell selection in human PSC populations in vivo and in vitro and we highlight the implications of understanding this phenomenon for human development and regenerative medicine.
AB - A small number of pluripotent cells within early embryo gives rise to all cells in the adult body, including germ cells. Hence, any mutations occurring in the pluripotent cell population are at risk of being propagated to their daughter cells and could lead to congenital defects or embryonic lethality and pose a risk of being transmitted to future generations. The observation that genetic errors are relatively common in preimplantation embryos, but their levels reduce as development progresses, suggests the existence of mechanisms for clearance of aberrant, unfit or damaged cells. Although early human embryogenesis is largely experimentally inaccessible, pluripotent stem cell (PSC) lines can be derived either from the inner cell mass (ICM) of a blastocyst or by reprogramming somatic cells into an embryonic stem cell-like state. PSCs retain the ability to differentiate into any cell type in vitro and, hence, they represent a unique and powerful tool for studying otherwise intractable stages of human development. The advent of PSCs has also opened up a possibility of developing regenerative medicine therapies, either through PSC differentiation in vitro or by creating interspecies chimeras for organ replacement. Here, we discuss the emerging evidence of cell selection in human PSC populations in vivo and in vitro and we highlight the implications of understanding this phenomenon for human development and regenerative medicine.
KW - Cell competition
KW - Human pluripotent stem cells
KW - Interspecies chimeras
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U2 - 10.1016/j.ydbio.2021.03.025
DO - 10.1016/j.ydbio.2021.03.025
M3 - Article
C2 - 33891964
AN - SCOPUS:85104871002
SN - 0012-1606
VL - 476
SP - 209
EP - 217
JO - Developmental Biology
JF - Developmental Biology
ER -