scispace - formally typeset
Search or ask a question
Author

Xiaosu Li

Bio: Xiaosu Li is an academic researcher from Fudan University. The author has contributed to research in topics: Neural stem cell & Olfactory bulb. The author has an hindex of 8, co-authored 13 publications receiving 301 citations. Previous affiliations of Xiaosu Li include State University of New York Upstate Medical University.

Papers
More filters
Journal ArticleDOI
TL;DR: It is shown that SVZ neuroblasts give rise almost exclusively to calretinin-expressing cells in the damaged striatum, resulting in the accumulation of these cells during long term recovery after stroke, and suggests that adult neuroblast do not alter their intrinsic differentiation potential after brain injury.
Abstract: Neuroblasts produced by the neural stem cells of the adult subventricular zone (SVZ) migrate into damaged brain areas after stroke or other brain injuries, and previous data have suggested that they generate regionally appropriate new neurons. To classify the types of neurons produced subsequent to ischemic injury, we combined BrdU or virus labeling with multiple neuronal markers to characterize new cells at different times after the induction of stroke. We show that SVZ neuroblasts give rise almost exclusively to calretinin-expressing cells in the damaged striatum, resulting in the accumulation of these cells during long term recovery after stroke. The vast majority of SVZ neuroblasts as well as newly born young and mature neurons in the damaged striatum constitutively express the transcription factor Sp8, but do not express transcription factors characteristic of medium-sized spiny neurons, the primary striatal projection neurons lost after stroke. Our results suggest that adult neuroblasts do not alter their intrinsic differentiation potential after brain injury.

112 citations

Journal ArticleDOI
TL;DR: Although the majority of OB interneuron subtypes continue to be generated throughout life, most subtypes show a similar “bell-like” temporal production pattern with a peak around birth, which suggests that Sp8 is required for the normal production of PV+ interneurons in the EPL of the OB.
Abstract: Interneurons in the olfactory bulb (OB) represent a heterogeneous population, which are first produced at embryonic stages and persisting into adulthood. Using the BrdU birthdating method combined with immunostaining for several different neuronal markers, we provide the integrated temporal patterns of distinct mouse OB interneuron production from embryonic day 14 to postnatal day 365. We show that although the majority of OB interneuron subtypes continue to be generated throughout life, most subtypes show a similar “bell-like” temporal production pattern with a peak around birth. Tyrosine hydroxylase and calretinin-expressing interneurons are produced at a relatively low rate in the adult OB, while parvalbumin-expressing (PV+) interneuron production is confined to later embryonic and early postnatal stages. We also show that Dlx5/6− expressing progenitors contribute to PV+ interneurons in the OB. Interestingly, all PV+ interneurons in the external plexiform layer (EPL) express the transcription factor Sp8. Genetic ablation of Sp8 by cre/loxP based recombination severely reduces the number of PV+ interneurons in the EPL of the OB. Our results suggest that Sp8 is required for the normal production of PV+ interneurons in the EPL of the OB. These data expand our understanding of the temporal and molecular regulation of OB interneuron neurogenesis.

53 citations

Journal ArticleDOI
TL;DR: In this article, a single-cell RNA-Seq with intersectional lineage analyses was used to reveal the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocyte and Olfactory bulb interneurons.
Abstract: Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1+EGFR+ apical multipotent intermediate progenitors (MIPCs), which then differentiate into basal MIPCs that express ASCL1, EGFR, OLIG2, and MKI67. These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons. Finally, single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons. Taken together, this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.

37 citations

Journal ArticleDOI
TL;DR: Genetic fate mapping reveals that newly born CR+ interneurons are generated from Emx1‐expressing neural stem cells in the dorsal–lateral SVZ, suggesting that the fate of the EmX1‐ expressing lineage in the ischemic damaged striatum is restricted.
Abstract: Neural stem cells from different regions within the subventricular zone (SVZ) are able to produce several different subtypes of interneurons in the olfactory bulb throughout life. Previous studies have shown that ischemic stroke induces the production of new neurons in the damaged striatum from the SVZ. However, the origins and genetic profiles of these newborn neurons remain largely unknown as SVZ neural stem cells are heterogeneous. In the present study, using a mouse model of perinatal hypoxic-ischemic (H/I) brain injury combined with BrdU labeling methods, we found that, as in rat brains, virtually all newborn neuroblasts that migrate from the SVZ into the ischemic injured striatum exclusively express the transcription factor Sp8. Furthermore, although newborn neuroblasts are plentiful in the damaged striatum, only a few can differentiate into calretinin-expressing (CR+) interneurons that continuously express Sp8. Genetic fate mapping reveals that newly born CR+ interneurons are generated from Emx1-expressing neural stem cells in the dorsal-lateral SVZ. These results suggest that the fate of the Emx1-expressing lineage in the ischemic damaged striatum is restricted. However, when Sp8 was conditionally inactivated in the Emx1-lineage cells, Pax6 was ectopically expressed by a subpopulation of Emx1-derived CR+ cells in the normal and damaged striatum. Interestingly, these cells possessed large cell bodies and long processes. This work identifies the origin of the newly born CR+ interneurons in the damaged striatum after ischemic brain injury.

34 citations

Journal ArticleDOI
TL;DR: It is demonstrated that Sonic hedgehog signaling is both necessary and sufficient for the generation of GSX2+ IPCs by reducing GLI3R protein levels and the process of the lineage switch of cortical NSCs.

34 citations


Cited by
More filters
Journal ArticleDOI
27 Feb 2014-Cell
TL;DR: It is shown that in adult humans new neurons integrate in the striatum, which is adjacent to this neurogenic niche, and this findings demonstrate a unique pattern of neurogenesis in the adult human brain.

821 citations

Journal ArticleDOI
TL;DR: The effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI) are focused on.

425 citations

Journal ArticleDOI
TL;DR: It is shown that adult zebrafish can efficiently regenerate brain lesions and lack permanent glial scarring, and regeneration after traumatic lesion of the adultZebrafish brain occurs efficiently from radial glia-type stem/progenitor cells.
Abstract: Severe traumatic injury to the adult mammalian CNS leads to life-long loss of function. By contrast, several non-mammalian vertebrate species, including adult zebrafish, have a remarkable ability to regenerate injured organs, including the CNS. However, the cellular and molecular mechanisms that enable or prevent CNS regeneration are largely unknown. To study brain regeneration mechanisms in adult zebrafish, we developed a traumatic lesion assay, analyzed cellular reactions to injury and show that adult zebrafish can efficiently regenerate brain lesions and lack permanent glial scarring. Using Cre-loxP-based genetic lineage-tracing, we demonstrate that her4.1-positive ventricular radial glia progenitor cells react to injury, proliferate and generate neuroblasts that migrate to the lesion site. The newly generated neurons survive for more than 3 months, are decorated with synaptic contacts and express mature neuronal markers. Thus, regeneration after traumatic lesion of the adult zebrafish brain occurs efficiently from radial glia-type stem/progenitor cells.

392 citations

Journal ArticleDOI
TL;DR: In Drosophila melanogaster and in mammalian neural stem and progenitor cells, these mechanisms are intricately coordinated with the developmental age and the nutritional, metabolic and hormonal state of the animal.
Abstract: Neural circuit function can be drastically affected by variations in the number of cells that are produced during development or by a reduction in adult cell number owing to disease. For this reason, unique cell cycle and cell growth control mechanisms operate in the developing and adult brain. In Drosophila melanogaster and in mammalian neural stem and progenitor cells, these mechanisms are intricately coordinated with the developmental age and the nutritional, metabolic and hormonal state of the animal. Defects in neural stem cell proliferation that result in the generation of incorrect cell numbers or defects in neural stem cell differentiation can cause microcephaly or megalencephaly.

285 citations

Journal ArticleDOI
TL;DR: By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms, and new treatment strategies need to be investigated.
Abstract: This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.

271 citations