Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain.
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.
Zeng
Xiao Xia
XX
Institute of Medical Biology, Singapore, Singapore.
Tan
Kian Hwa
KH
Yeo
Ailing
A
Sasajala
Piriya
P
Tan
Xiaowei
X
Xiao
Zhi Cheng
ZC
Dawe
Gavin
G
Udolph
Gerald
G
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