Different States and Different Populations of Neural Stem Cells in the Adult Hippocampus

Adult stem cell;clonal lineage tracing;Human Genetics and Molecular Biology

Stadel, Ryan PValle, David ;

Johns Hopkins University

关键词: Adult stem cell;    clonal lineage tracing;    Human Genetics and Molecular Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60529/STADEL-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Over the past couple of decades, a central dogma in neuroscience has been overturned, the belief that no new neurons are generated in the adult mammalian brain.It has now been shown that within discrete regions there is generation and incorporation of new neurons in the adult brain, including humans.The origins of these newborn cells as well as whether a bona fide adult neural stem cell exists is, however, under intense debate.Hallmark properties of individual stem cells include repeated self-renewal and the potential of differentiation into specialized cells.Complex stem cell behavior, however, has led to uncertainty regarding their identities, basic characteristics and relationships in multiple somatic tissues.Recent development of clonal lineage-tracing of individual cells has revealed a population of quiescent radial glia-like neural stem cells (RGLs) marked by Nestin-CreERT2 (Nestin#) in the adult mouse hippocampus.Whether Nestin# RGLs represent the only, homogeneous population of stem cells in the adult SGZ remains unclear.In my thesis, we performed clonal lineage-tracing of RGLs marked by Gli1-CreERT2 (Gli1#) and Ascl1-CreERT2 (Ascl1#). Both RGLs exhibit stem cell characteristics, but differ in their self-renewal modes and cell cycle properties.Time-course and computational analyses suggest that Gli1# marks the stochastic, multipotent Nestin#-RGL population in a pre-activation state, whereas Ascl1#-RGLs represent a distinct, neuronal fate biased population.Furthermore, Gli1#-RGLs and Nestin#-RGLs acquire Ascl1#-RGL-like properties upon injury.My study resolves dynamic behavior of apparent similar stem cells into different states of the same population and discrete populations that co-exist in the same tissue.