title: Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain.
abstract: Bidirectional cell trafficking between fetus and mother during pregnancy is a well-established phenomenon observed in placental vertebrates including humans. Although studies have shown that transmigratory fetal cells, also termed pregnancy-associated progenitor cells (PAPCs), can integrate into multiple maternal organs, the integration, long-term survival, and differentiation of PAPCs in the brain has not been extensively studied. Using a murine model of fetomaternal microchimerism, we show that PAPCs integrated and persisted in several areas of the maternal brain for up to 7 months postpartum. Besides expressing neural stem cell or immature neuronal markers, PAPCs were observed to express mature neuronal markers, indicating that PAPCs adopted a neuronal fate. Further, PAPCs also displayed morphologically neuronal maturation by an increasing axonal/dendritic complexity over time. Therefore, PAPCs seem to undergo a molecular and morphological maturation program similar to that observed during adult neurogenesis. We provide evidence that neuronal gene expression of PAPCs was not a consequence of cell fusion with maternal neurons. In addition, in mothers with experimentally induced Parkinson's disease (PD), the frequency of PAPCs within the hippocampus initially increased whereas long-term presence of PAPCs was compromised. Also, the spatial distribution of PAPCs within the hippocampus was altered in mothers with PD. Thus, the disease context influenced the initial attraction, long-term survival, and spatial distribution of PAPCs, which may have wider implications on cell replacement strategies in human neurodegenerative diseases such as PD.
authors: Institute of Medical Biology, Singapore, Singapore.
authors: Xiao Xia
authors: XX
authors: Zeng
authors: Kian Hwa
authors: KH
authors: Tan
authors: Ailing
authors: A
authors: Yeo
authors: Piriya
authors: P
authors: Sasajala
authors: Xiaowei
authors: X
authors: Tan
authors: Zhi Cheng
authors: ZC
authors: Xiao
authors: Gavin
authors: G
authors: Dawe
authors: Gerald
authors: G
authors: Udolph
mesh_terms: D000818:Animals; D002465:Cell Movement; D046528:Chimerism; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008431:Maternal-Fetal Exchange; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy