Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research.
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.
School of Medicine, Washington University in St. Louis, St. Louis, USA.
Mary G
MG
Dandulakis
Department of Developmental Biology, Washington University in St. Louis, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110-1093 USA.
Kesavan
K
Meganathan
Department of Developmental Biology, Washington University in St. Louis, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110-1093 USA.
Kristen L
KL
Kroll
Department of Neuroscience, Washington University in St. Louis, Campus Box 8108, 660 S. Euclid Ave., St. Louis, MO 63110-1093 USA.
Azad
A
Bonni
Department of Psychiatry, Washington University in St. Louis, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO 63110 USA.
John N
JN
Constantino
ASD; Autism; Developmental disorders; X chromosome; X-inactivation; X-linked ASD; X-reactivation; iPSC; “Female protective effect”