ABSTRACT
Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identified molecular markers of pregnancy-associated interneurons and showed that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient yet behaviorally relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity.
Subject(s)
Interneurons , Lateral Ventricles , Maternal Behavior , Neurogenesis , Neuronal Plasticity , Olfactory Bulb , Pregnancy , Smell , Animals , Female , Mice , Pregnancy/physiology , Adult Stem Cells/physiology , Interneurons/cytology , Interneurons/physiology , Lateral Ventricles/cytology , Lateral Ventricles/growth & development , Neural Stem Cells/physiology , Neurogenesis/physiology , Olfactory Bulb/cytology , Olfactory Bulb/growth & development , Olfactory Bulb/metabolism , Transcriptome , Maternal Behavior/physiologyABSTRACT
The ventricular-subventricular zone (V-SVZ) harbors adult neural stem cells. V-SVZ neural stem cells exhibit features of astrocytes, have a regional identity, and depending on their location in the lateral or septal wall of the lateral ventricle, generate different types of neuronal and glial progeny. We performed large-scale single-cell RNA sequencing to provide a molecular atlas of cells from the lateral and septal adult V-SVZ of male and female mice. This revealed regional and sex differences among adult V-SVZ cells. We uncovered lineage potency bias at the single-cell level among lateral and septal wall astrocytes toward neurogenesis and oligodendrogenesis, respectively. Finally, we identified transcription factor co-expression modules marking key temporal steps in neurogenic and oligodendrocyte lineage progression. Our data suggest functionally important spatial diversity in neurogenesis and oligodendrogenesis in the adult brain and reveal molecular correlates of adult NSC dormancy and lineage specialization.
Subject(s)
Cell Lineage , Lateral Ventricles/cytology , Neural Stem Cells/cytology , Single-Cell Analysis/methods , Transcriptome , Animals , Astrocytes/cytology , Astrocytes/metabolism , Female , Male , Mice , Mice, Inbred C57BL , Neural Stem Cells/metabolism , Neurogenesis , Neurons/cytology , Neurons/metabolism , Organ SpecificityABSTRACT
This study describes an ultrathin-layer sodium dodecyl sulfate (SDS) disc electrophoresis in polyacrylamide gels of a thickness of only 150 microm. By use of 2-amino-2-methyl-1,3-propanediol/glycine instead of traditional Tris/HCl buffer in the resolving phase of the gel, proteins with a wide range of molecular sizes (10 kDa to over 220 kDa) are separated in unusually low-concentrated gels (4%T, 3.3%C). 2-Amino-2-methyl-1,3-propanediol in the resolving part of the gel contributes to stabilization of the pH value at 8.8, while glycine improves destacking as well as separation of small proteins from the bulk of stacked SDS. This method combines both the advantages of conventional slab-gel electrophoresis and capillary gel electrophoresis. It is easy to apply and well suited for all further miniaturization attempts.
Subject(s)
Electrophoresis, Polyacrylamide Gel/methods , Proteins/isolation & purification , Animals , Buffers , Electrophoresis, Polyacrylamide Gel/instrumentation , Electrophoresis, Polyacrylamide Gel/standards , Gels , Microchemistry/instrumentation , Microchemistry/methods , Molecular Weight , RatsABSTRACT
The distribution pattern of "testis-specific aldehyde dehydrogenase" in mouse tissues was investigated. Because of the broad substrate specificity and the high degree of sequence identity of the large aldehyde dehydrogenase family a specific detection of single isoforms is not possible by histochemical means. Therefore, the technique of native isoelectric focusing was used. Thus, the expression of four to five banded "testis-specific aldehyde dehydrogenase" in the mouse testis was confirmed. However, the activity of this enzyme with the same pattern of multiplicity was found not only in the testis but also in the uterus and in embryonic tissues. At 9.5 and 10.5 days of embryonic development the enzyme activity was restricted to tissues of the embryonic trunk and absent in extracts from cranial tissues. The tissue distribution as well as substrate specificity and isoelectric points indicate that the "testis-specific aldehyde dehydrogenase" corresponds to mouse type 2 retinaldehyde dehydrogenase.
