Region-Restrict Astrocytes Exhibit Heterogeneous Susceptibility to Neuronal Reprogramming

Hu, Xiangyou; Qin, Shangyao; Huang, Xu; Yuan, Yihang; Tan, Zijian; Gu, Yakun; Cheng, Xueyan; Wang, Dan; Lian, Xiaojuan; He, Cheng; Su, Zhida

doi:10.1016/j.stemcr.2018.12.017

Cited by 44 publications

(45 citation statements)

References 49 publications

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“…This satellite glia signature gene set included known satellite glia markers such as Kcnj10/Kir4.1 and Glul, as well as Bcan, Cxcr4,Fgfr1,Nrarp,Adamts5,Hmgcs1,Cst3,Atp1b2 and Glast1 ( Figure 5B). Interestingly, these genes are also characteristically expressed in astrocytes (Anlauf and Derouiche, 2013;Bachoo et al, 2004;Batiuk et al, 2017;Cali and Bezzi, 2010;Clarke et al, 2001;Demircan et al, 2013;Hu et al, 2019;Itoh et al, 2018;Shibata et al, 1997;Tong et al, 2014;, suggesting functional similarities between satellite glia and astrocytes, as highlighted recently (Avraham et al, 2020).…”

Section: Satellite Glia In Drg and Cochlea Differ From One Anothermentioning

confidence: 52%

Diversity of developing peripheral glia revealed by single cell RNA sequencing

Tasdemir-Yilmaz

Druckenbrod

Olukoya

et al. 2020

Preprint

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The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse peripheral sensory neurons are closely associated with glial cells that originate from the neural crest (NC). However, the molecular nature and origins of diversity among peripheral glia is not understood. Here we used single cell RNA sequencing to profile and compare developing and mature glia from somatosensory lumbar dorsal root ganglia (DRG) and auditory spiral ganglia (SG). We found that the glial precursors (GPs) differ in their transcriptional profile and prevalence in these two systems. Despite their unique features, somatosensory and auditory GPs undergo convergent differentiation to generate myelinating and non-myelinating Schwann cells that are molecularly uniform. By contrast, although satellite glia surround the neuronal cell bodies in both ganglia, we found that those in the SG express multiple myelination-associated genes, while DRG satellite cells express components that suppress myelination. Lastly, we identified a set of glial signature genes that are also expressed by placode-derived supporting cells, providing new insights into commonalities among glia across the nervous system. This comprehensive survey of gene expression in peripheral glia constitutes a valuable resource for understanding how glia acquire specialized functions and how their roles differ across sensory modalities.

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Section: Satellite Glia In Drg and Cochlea Differ From One Anothermentioning

confidence: 52%

Diversity of developing peripheral glia revealed by single cell RNA sequencing

Tasdemir-Yilmaz

Druckenbrod

Olukoya

et al. 2020

Preprint

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“…Finally, the rapid evolution of sequencing techniques has made the term "astrocyte" an umbrella-like category for a group of highly heterogeneous cells [13,184,185,216]. Though there is some in vivo evidence that astrocytes can become locally specialized to provide circuitspecific support [13], this remains an open area ripe for future investigation.…”

Section: Discussionmentioning

confidence: 99%

The role of astrocyte‐mediated plasticity in neural circuit development and function

2021

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Neuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.

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“…In their study, it showed that NGN2 overexpression generated GABAergic neurons in the striatum while generating glutamatergic neurons in the neocortex. In addition, Hu et al 38 reported that astrocytes derived from the cortex, cerebellum, and spinal cord exhibited biological heterogeneity and possessed distinct susceptibility to transcription factor-induced neuronal reprogramming. Based on those studies and our results, we hypothesized that the intrinsic properties of astrocytes from different brain regions and the local environment niche together contribute to the generation of different neuronal subtypes.…”

Section: Discussionmentioning

confidence: 99%

In vivo chemical reprogramming of astrocytes into neurons

Xie

et al. 2021

Cell Discov

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In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.

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Region-Restrict Astrocytes Exhibit Heterogeneous Susceptibility to Neuronal Reprogramming

Cited by 44 publications

References 49 publications

Diversity of developing peripheral glia revealed by single cell RNA sequencing

Diversity of developing peripheral glia revealed by single cell RNA sequencing

The role of astrocyte‐mediated plasticity in neural circuit development and function

In vivo chemical reprogramming of astrocytes into neurons

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