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RISS 인기검색어
- 검색키워드
- 저자 : Sidman, Richard L. (검색결과 2 건)
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Expression profile of an operationally-defined neural stem cell clone
Parker, Mark A.,Anderson, Julia K.,Corliss, Deborah A.,Abraria, Victoria E.,Sidman, Richard L.,Park, Kook In,Teng, Yang D.,Cotanche, Douglas A.,Snyder, Evan Y. Elsevier 2005 Experimental neurology Vol.194 No.2
<P><B>Abstract</B></P><P>Neural stem cells (NSCs) are the most primordial and least committed cells of the nervous system, the cells that exist <I>before</I> regional specification develops. Because immunocytochemically-detectable markers that are sufficiently specific and sensitive to define an NSC have not yet been fully defined, we have taken the strong view that, to be termed a “stem cell” in the nervous system—in contrast to a “progenitor” or “precursor” (whose lineage commitment is further restricted)—a <I>single neuroectodermally-derived cell</I> must fulfill an operational definition that is essentially similar to that used in hematopoiesis. In other words, it must possess the following functional properties: (1) “Multipotency”, i.e., the ability to yield mature cells in all three fundamental neural lineages throughout the nervous system—neurons (of all subtypes), astrocytes (of all types), oligodendrocytes—in multiple regional and developmental contexts and in a region and developmental stage-appropriate manner. (2) The ability to populate a developing region and/or repopulate an ablated or degenerated region of the nervous system with appropriate cell types. (3) The ability to be serially transplanted. (4) “Self-renewal”, i.e., the ability to produce daughter cells (including new NSCs) with identical properties and potential. Having identified a murine neural cell clone that fulfills this strict operational definition—in contrast to other studies that used less rigorous or non-operational criteria for defining an NSC (e.g., the “neurosphere” assay)—we then examined, by comparing gene expression profiles, the relationship such a cell might have to (a) a <I>multipotent</I> somatic stem cell from another organ system (the hematopoietic stem cell [HSC]); (b) a <I>pluripotent</I> stem cell derived from the inner cell mass and hence without organ assignment (an embryonic stem cell); (c) neural cells isolated and maintained primarily as neurospheres but without having been subjected to the abovementioned operational screen (“CNS-derived neurospheres”). ESCs, HSCs, and operationally-defined NSCs—all of which have been identified not only by markers but by functional assays in their respective systems and whose state of differentiation could be synchronized—shared a large number of genes. Although, as expected, the most stem-like genes were expressed by ESCs, NSCs and HSCs shared a number of genes. CNS-derived neurospheres, on the other hand, expressed fewer “stem-like” genes held in common by the other operationally-defined stem cell populations. Rather they displayed a profile more consistent with differentiated neural cells. (Genes of neural identity were shared with the NSC clone.) Interestingly, when the operationally-defined NSC clone was cultured as a neurosphere (rather than in monolayer), its expression pattern shifted from a “stem-like” pattern towards a more “differentiated” one, suggesting that the neurosphere, without functional validation, may be a poor model for predicting stem cell attributes because it consists of heterogeneous populations of cells, only a small proportion of which are truly “stem-like”. Furthermore, when operational definitions are employed, a common set of stem-like genes does emerge across both embryonic and somatic stem cells of various organ systems, including the nervous system.</P>
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In Park, Kook,Hack, Michael A.,Ourednik, Jitka,Yandava, Booma,Flax, Jonathan D.,Stieg, Philip E.,Gullans, Stephen,Jensen, Francis E.,Sidman, Richard L.,Ourednik, Vaclav,Snyder, Evan Y. Elsevier 2006 Experimental neurology Vol.199 No.1
<P><B>Abstract</B></P><P>Clonal neural cells with stem-like features integrate appropriately into the developing and degenerating central and peripheral nervous system throughout the neuraxis. In response to hypoxic–ischemic (HI) injury, previously engrafted, integrated, and quiescent clonal neural stem cells (NSCs) transiently re-enter the cell cycle, migrate preferentially to the site of ischemia, and differentiate into neurons and oligodendrocytes, the neural cell types typically lost following HI brain injury. They also replenish the supply of immature uncommitted resident stem/progenitor cells. Although they yield astrocytes, scarring is inhibited. These responses appear to occur most robustly within a 3–7 day “window” following HI during which signals are elaborated that upregulate genetic programs within the NSC that mediate proliferation, migration, survival, and differentiation, most of which appear to be terminated once the “window closes” and the chronic phase ensues, sending the NSCs into a quiescent state. These insights derived from using the stem cell in a novel role – as a “reporter” cell – to both track and probe the activity of endogenous stem cells as well as to “interrogate” and “report” the genes differentially induced by the acutely vs. chronically injured milieu. NSCs may be capable of the replacement of cells, genes, and non-diffusible factors in both a widespread or more circumscribed manner (depending on the therapeutic demands of the clinical situation). They may be uniquely responsive to some types of neurodegenerative conditions. We submit that these various capabilities are simply the normal expression of the basic homeostasis-preserving biologic properties and attributes of a stem cell which, if used rationally and in concert with this biology, may be exploited for therapeutic ends.</P>
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