Neural Stem Cells in Adult Mammals are not Astrocytes

Velloso, Fernando Janczur; Shankar, Sandhya; Parpura, Vladimir; Rakić, Paško; Levison, Steven W.

doi:10.1177/17590914221134739

Cited by 9 publications

(5 citation statements)

References 137 publications

(213 reference statements)

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“…The numbers of astrocytes, but not of microglia, were increased in AD, albeit not in a statistically signi cant manner (Figure 2A,B). Notably, previous attempts have been made to discriminate between NSCs and astrocytes in the rodent and human brains [35][36][37] . Our snRNAseq-based sequencing, machine-learning analysis and cell annotation based on both developmental and adult human hippocampal dataset revealed distinct clusters of mature astrocytes and NSCs (Figure 1B).…”

Section: Characteristics Of Neurogenesis In the Human Brainmentioning

confidence: 99%

A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

Lazarov,

Disouky,

Sanborn

et al. 2024

Preprint

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In the rodent, hippocampal neurogenesis plays critical roles in learning and memory 1,2, is tightly regulated by inhibitory neurons 3-7 and contributes to memory dysfunction in Alzheimer’s disease (AD) mouse models 8-10. In contrast, the mechanisms regulating neurogenesis in the adult human hippocampus, the dynamic shifts in the transcriptomic and epigenomic profiles in aging and AD and putative niche interactions within the cellular environment, remain largely unknown. Using single nuclei multi-omics of postmortem human hippocampi we map the molecular mechanisms of hippocampal neurogenesis across aging, cognitive decline, and AD neuropathology. Transcriptomic and epigenetic profiling of neural stem cells (NSCs), neuroblasts and immature neurons suggests that the earliest shift in the characteristics of neurogenesis takes place in NSCs in aging. Cognitive impairment was associated with changes in neuroblast profile. In AD, there was a widespread cessation of the transcription machinery in immature neurons, with robust downregulation of genes regulating ribosomal and mitochondrial function. Further, there was substantial loss of parvalbumin+ inhibitory neurons in the hippocampus in aging. The number of the rest of inhibitory neurons were reduced as a function of age and diagnosis. Notably, a similar system-level effect was observed between immature and inhibitory neurons in the transition from aging to AD, manifested by common molecular pathways that were ultimately lost in AD. The numbers of neuroblasts, immature and GABAergic neurons inversely correlated with extent of neuropathology. Using CellChat and NeuronChat, we inferred the ligands and receptors by which neurogenic cells communicate with their cellular environment. Loss of synaptic adhesion molecules and neurotransmitters, either sent or received by neurogenic cells, was observed in AD. Together, this study delineates the molecular mechanisms and dynamics of human neurogenesis, functional association with inhibitory neurons and a mechanism of hippocampal hyperexcitability in AD.

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Section: Characteristics Of Neurogenesis In the Human Brainmentioning

confidence: 99%

A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

Lazarov,

Disouky,

Sanborn

et al. 2024

Preprint

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“…and cells lining the wall of ventricles (ependymocytes, choroids plexus cells) 13 . Recently, astroglial nature of adult brain stem cells has been questioned, 14 without, in our view, strong rationale. Structurally, RSA present radial morphology, being thus distinct from protoplasmic astrocytes.…”

Section: A Note Of the Nomenclaturementioning

confidence: 99%

Radial stem astrocytes (aka neural stem cells): Identity, development, physio‐pathology, and therapeutic potential

Yeh

Huang

et al. 2023

Acta Physiologica

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Adult neurogenesis is a striking example of neuroplasticity, which enables adaptive network remodelling in response to all forms of environmental stimulation in physiological and pathological contexts. Dysregulation or cessation of adult neurogenesis contributes to neuropathology negatively affecting brain functions and hampering regeneration of the nervous tissue while targeting adult neurogenesis may provide the basis for potential therapeutic interventions. Neural stem cells in the adult mammalian brain are at the core and the entry point of adult neurogenesis. By their origin and properties, these cells belong to astroglia, and are represented by stem radial astrocytes (RSA) which exhibit multipotent “stemness”. In the neurogenic niches, RSA interact with other cellular components, including protoplasmic astrocytes, which in turn regulate their neurogenic activity. In pathology, RSA become reactive, which affects their neurogenic capabilities, whereas reactive parenchymal astrocytes up‐regulate stem cell hallmarks and are able to generate progeny that remain within astrocyte lineage. What makes RSA special is their multipotency, represented by self‐renewing capacity capability to generate other cellular types as progeny. A broad understanding of the cellular features of RSA and parenchymal astrocytes provides an insight into the machinery that promotes/suppresses adult neurogenesis, clarifying principles of network remodelling. In this review, we discuss the cellular hallmarks, research tools, and models of RSA and astrocytes of the subventricular zone along the lateral ventricle and dentate gyrus of the hippocampus. We also discuss RSA in ageing, which has a great impact on the proliferative capacity of RSA, as well as the potential of RSA and astrocytes in therapeutic strategies aimed at cell replacement and regeneration.

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“…Several studies assessing the effectiveness of stem cells in treating TBI have been conducted [7,8]. Neural stem cells (NSCs) have a self-renewal ability and can differentiate into mature neurons [9,10]. Studies on the effectiveness of NSCs in treating TBI in rodents have shown that transplanted NSCs can survive and differentiate into neurons and then partially replace the damaged neurons, resulting in improved motor function after TBI, that a study in TBI rat models showed that NSCs are capable of surviving engraftment and differentiating into neurons which, in turn, correlate with improvements in neurological recovery [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Neural Stem Cells Transplanted into Rhesus Monkey Cortical Traumatic Brain Injury Can Survive and Differentiate into Neurons

Liu,

Shi,

Huang

et al. 2024

IJMS

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Cortical traumatic brain injury (TBI) is a major cause of cognitive impairment accompanied by motor and behavioral deficits, and there is no effective treatment strategy in the clinic. Cell transplantation is a promising therapeutic strategy, and it is necessary to verify the survival and differentiation of cells after transplantation in large animal models like rhesus monkeys. In this study, we transplanted neural stem cells (NSCs) and simultaneously injected basic fibroblast growth factor/epidermal growth factor (bFGF/EGF) into the cortex (visual and sensory cortices) of rhesus monkeys with superficial TBI. The results showed that the transplanted NSCs did not enter the cerebrospinal fluid (CSF) and were confined to the transplantation site for at least one year. The transplanted NSCs differentiated into mature neurons that formed synaptic connections with host neurons, but glial scar formation between the graft and the host tissue did not occur. This study is the first to explore the repairing effect of transplanting NSCs into the superficial cerebral cortex of rhesus monkeys after TBI, and the results show the ability of NSCs to survive long-term and differentiate into neurons, demonstrating the potential of NSC transplantation for cortical TBI.

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Neural Stem Cells in Adult Mammals are not Astrocytes

Cited by 9 publications

References 137 publications

A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

Radial stem astrocytes (aka neural stem cells): Identity, development, physio‐pathology, and therapeutic potential

Neural Stem Cells Transplanted into Rhesus Monkey Cortical Traumatic Brain Injury Can Survive and Differentiate into Neurons

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