The Origin And Differentiation Of Microglia In Transplants Of Embryonic Cortical Tissue

The adult brain has a limited capacity of self-repairing after neuronal loss caused by trauma or disease.Many experimental studies have explored the possibility to restore the lost functions by replacing damaged brain area with embryonic cortical tissues to reestablish neuronal network and improve cortical function of the host brain.For a successful transplantation,the entire cell populations of cortical tissue including neurons and different subsets of glial cells have to be reestablished.However,previous studies mostly focused on the survival and development of grafted neurons,and little information was available regarding the other essential cell subsets in cortical tissue.One of the key cell subsets that may affect the survival of graft tissue and reestablishment of synaptic connections is microglia.As the immunocompetent cells in the central nervous system,microglia show remarkable functional diversity under different conditions in brain.Activated microglia can derive from different sources in different neuropathological conditions in adult brain.The dynamics and sources of microglia are well described in healthy and diseased brain,but it is still undefined about the microglial activation and population dynamics in grafted embryonic tissue.In this study,we took advantage of transgenic mice that express green fluorescent protein(GFP)in microglia and in vivo two-photon imaging to investigate the survival of endogenous microglia and the infiltration,repopulation and differentiation of host-derived microglia in an embryonic cortical tissue transplantation model.A parabiosis model was used to determine the fate and origin of both endogenous and host-derived microglia after successful transplantation.Our data showed that grafted neurons can survive and differentiate in the host brains.Unlike the graft neurons,the endogenous microglia of the grafted tissue were rapidly lost after transplantation.Instead,distribution of the Iba-1 positive microglia in the transplants were derived from host.Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain.Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiating into resting ramified morphology.Collectively,our data demonstrated that host-derived microglia infiltrated into the graft and restored the microglial population in the transplanted tissue and local resident microglia in host brain parenchyma was the main source of colonized microglia.