TY - JOUR
T1 - Complexities of X chromosome inactivation status in female human induced pluripotent stem cells - A brief review and scientific update for autism research
AU - Dandulakis, Mary G.
AU - Meganathan, Kesavan
AU - Kroll, Kristen L.
AU - Bonni, Azad
AU - Constantino, John N.
N1 - Funding Information:
The research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number U54 HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University, the NIH T35 NHLBI training grant, and the NCBI award number NIHR01GM66815. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/6/9
Y1 - 2016/6/9
N2 - Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully represent an individual's genetic background; therefore, in the absence of available human brain tissue from a living patient, these models have a significant advantage relative to other models of neurodevelopmental disease. When using human induced pluripotent stem cells (hiPSCs) to model X-linked developmental disorders or inherited conditions that undergo sex-specific modulation of penetrance (e.g., autism spectrum disorders), there are significant complexities in the course and status of X chromosome inactivation (XCI) that are crucial to consider in establishing the validity of cellular models. There are major gaps and inconsistencies in the existing literature regarding XCI status during the derivation and maintenance of hiPSCs and their differentiation into neurons. Here, we briefly describe the importance of the problem, review the findings and inconsistencies of the existing literature, delineate options for specifying XCI status in clonal populations, and develop recommendations for future studies.
AB - Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully represent an individual's genetic background; therefore, in the absence of available human brain tissue from a living patient, these models have a significant advantage relative to other models of neurodevelopmental disease. When using human induced pluripotent stem cells (hiPSCs) to model X-linked developmental disorders or inherited conditions that undergo sex-specific modulation of penetrance (e.g., autism spectrum disorders), there are significant complexities in the course and status of X chromosome inactivation (XCI) that are crucial to consider in establishing the validity of cellular models. There are major gaps and inconsistencies in the existing literature regarding XCI status during the derivation and maintenance of hiPSCs and their differentiation into neurons. Here, we briefly describe the importance of the problem, review the findings and inconsistencies of the existing literature, delineate options for specifying XCI status in clonal populations, and develop recommendations for future studies.
KW - ASD
KW - Autism
KW - Developmental disorders
KW - Female protective effect
KW - X chromosome
KW - X-inactivation
KW - X-linked ASD
KW - X-reactivation
KW - iPSC
UR - http://www.scopus.com/inward/record.url?scp=84974712458&partnerID=8YFLogxK
U2 - 10.1186/s11689-016-9155-8
DO - 10.1186/s11689-016-9155-8
M3 - Review article
C2 - 27303449
AN - SCOPUS:84974712458
SN - 1866-1947
VL - 8
JO - Journal of Neurodevelopmental Disorders
JF - Journal of Neurodevelopmental Disorders
IS - 1
M1 - 22
ER -