ABSTRACT
Neural stem (NS) cells are a self-renewing population of symmetrically dividing multipotent radial glia-like stem cells, characterized by homogeneous expansion in monolayer. Here we report that fetal NS cells isolated from different regions of the developing mouse nervous system behave in a similar manner with respect to self-renewal and neuropotency, but exhibit distinct positional identities. For example, NS cells from the neocortex maintain the expression of anterior transcription factors, including Otx2 and Foxg1, while Hoxb4 and Hoxb9 are uniquely found in spinal cord-derived NS cells. This molecular signature was stable for over 20 passages and was strictly linked to the developmental stage of the donor, because only NS cells derived from E14.5 cortex, and not those derived from E12.5 cortex, carried a consistent transcription factor profile. We also showed that traits of this positional code are maintained during neuronal differentiation, leading to the generation of electrophysiologically active neurons, even if they do not acquire a complete neurochemical identity.
Subject(s)
Fetus/cytology , Neural Stem Cells/metabolism , Animals , Cell Differentiation , Cells, Cultured , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Mice , Neocortex/cytology , Neocortex/embryology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Otx Transcription Factors/genetics , Otx Transcription Factors/metabolism , Patch-Clamp Techniques , Spinal Cord/cytology , Spinal Cord/embryology , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Neural stem (NS) cells are a homogenous population of stem cells that expands in monolayer under serum-free conditions while remaining highly neuropotent. Here, we generated NS cells from induced pluripotent stem (iPS) cells that were previously derived from mouse fibroblasts (NS-(f)iPS). We showed that NS-(f)iPS cells exhibit long-term expansion and express markers of neurogenic radial glia. Analyses of the regional markers expressed in NS-(f)iPS cells suggested a ventral-rhombencephalic identity. Upon exposure to differentiation protocols, NS-(f)iPS cells produce neurons, astrocytes, and oligodendrocytes with an efficiency similar to ES-derived NS cells. NS-(f)iPS cells represent a new tool for studying neural cell fate determination and terminal differentiation, providing an interesting resource for experimental transplantation. Comparative studies between NS cells derived from iPS cells, reprogrammed from different somatic sources, and from authentic ES cells are necessary to identify critical elements for multipotency acquisition.