A Cellular Taxonomy of the Adult Human Spinal Cord

Yadav, Archana; Matson, Kaya J.E.; Li, Li; Hua, Isabelle; Gaur, Pallavi; Hasan, Saadia; Galuta, Ahmad; Dedek, Annemarie; Ameri, Sara; Parnell, Jessica; Alshardan, Mohammed M; Ququmji, Feras A; Alhamad, Saud M.; Wang, Alick Pingbei; Poulen, Gaëtan; Lonjon, Nicolas; Vachiéry-Lahaye, Florence; Nalls, Mike A.; Qi, Yue; Hildebrand, Michael E.; Méry, Pierre‐François; Bourinet, Emmanuel; Bauchet, Luc; Tsai, Eve C.; Ward, Michael E.; Pichon, Claire Le; Menon, Vilas; Levine, Ariel J.

doi:10.1101/2022.03.25.485808

Cited by 14 publications

(17 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although in most CNS regions PV-expressing neurons are inhibitory, the dorsal horn represents a unique area in which the calcium buffer is also expressed in excitatory neurons (Häring et al, 2018; Sathyamurthy et al, 2018, Russ et al, 2021). This feature is not restricted to mice, as recent data from rhesus macaque (Arokiaraj et al, 2022) and human (Yadav et al, 2022) dorsal horns indicate that PV is expressed in both glutamatergic and GABAergic neuronal clusters. The percentage of excitatory and inhibitory neurons expressing PV has been studied in mice and is less consistent, varying from 50 to 95% inhibitory (Hughes et al, 2012; Petitjean et al, 2015; Abraira et al, 2017; Gradwell et al, 2022).…”

Section: Discussionmentioning

confidence: 93%

“…Recent advances in ISH and IHC on human spinal cord tissue (Shiers et al, 2021; Yadav et al, 2022; Arokiaraj et al, 2022; Dedek et al, 2022) provide the needed resources that will help validate our preclinical findings of inhibitory neurons. In the mouse, the dorsal horn is comprised of several subsets of inhibitory interneurons involved in modality-specific processing of peripheral inputs (Bourane et al, 2015a; Bourane et al, 2015b; Koch et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Parvalbumin protein controls inhibitory tone in the spinal cord

Qiu

Miraucourt

Petitjean

et al. 2022

Preprint

View full text Add to dashboard Cite

The nervous system processes sensory information by relying on the precise coordination of neuronal networks and their specific synaptic firing patterns. In the spinal cord, disturbances to the firing pattern of the tonic firing parvalbumin (PV)-expressing inhibitory interneuron (PV neurons) disrupt the ability of the dorsal horn to integrate touch information and may result in pathological phenotypes. The parvalbumin protein (PVp) is a calcium (Ca2+)-binding protein that buffers the accumulation of Ca2+ following a train of action potential to allow for tonic firing. Here, we find that peripheral nerve injury causes a decrease in PVp expression in PV neurons and makes them transition from tonic to adaptive firing. We also show that reducing the expression of PVp causes otherwise healthy adult mice to develop mechanical allodynia and causes their PV neurons to lose their high frequency firing pattern. We show that this frequency adaptation is mediated by activation of SK channels on PV neurons. Further, we show their tonic firing can be partially restored after nerve injury by selectively inhibiting the SK2 channels of PV neurons. We also reveal that a decrease in the transcriptional coactivator, PGC-1α causes decrease PVp expression and the development of mechanical allodynia. By preventing the decrease in PVp expression before nerve injury, we were able to protect mice from developing mechanical allodynia. Our results indicate an essential role for PVp-mediated calcium buffering in PV neuron firing activity and the development of mechanical allodynia after nerve injury.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Parvalbumin protein controls inhibitory tone in the spinal cord

Qiu

Miraucourt

Petitjean

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Of note, a similar integrative approach was used to create a harmonized atlas of mouse spinal cord cell types, but with limited details of OLs ( Russ et al, 2021 ). Lastly, a comprehensive cellular taxonomy of the adult human spinal cord was recently released by Yadav et al (2022) , including an integrative analysis of mouse and human data.…”

Section: Oligodendrocyte Heterogeneity In Healthmentioning

confidence: 99%

Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics

Valihrach

Matusova

Žucha

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Oligodendrocytes (OL) have been for decades considered a passive, homogenous population of cells that provide support to neurons, and show a limited response to pathological stimuli. This view has been dramatically changed by the introduction of powerful transcriptomic methods that have uncovered a broad spectrum of OL populations that co-exist within the healthy central nervous system (CNS) and also across a variety of diseases. Specifically, single-cell and single-nucleus RNA-sequencing (scRNA-seq, snRNA-seq) have been used to reveal OL variations in maturation, myelination and immune status. The newly discovered immunomodulatory role suggests that OL may serve as targets for future therapies. In this review, we summarize the current understanding of OL heterogeneity in mammalian CNS as revealed by scRNA-seq and snRNA-seq. We provide a list of key studies that identify consensus marker genes defining the currently known OL populations. This resource can be used to standardize analysis of OL related datasets and improve their interpretation, ultimately leading to a better understanding of OL functions in health and disease.

show abstract

“…While this work was in progress, a single cell RNA seq analysis was performed on seven lumbar spinal cords with some of the cases included in the present article and aged 50-80 years old. Results are released as a preprint manuscript and an associated browsable interface 22 . Using this gene expression database, we found that 6/7 of the genes we explored in our study by IHC, namely Arx, FoxJ1, Msx1, Pax6, Rfx2 and Sox2 were well expressed in ependymal cells at the single cell RNA level (fig.…”

Section: Resultsmentioning

confidence: 99%

Persistence of FoxJ1⁺ Pax6⁺ Sox2⁺ ependymal cells throughout life in the human spinal cord

Ripoll

Poulen

Chevreau

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Spinal cord ependymal cells have stem cell properties in mice. They surround the central canal and keep expressing spinal cord developmental transcription factors. Similar cells exist in young humans however their persistence with aging is debated. We clarified this issue by collecting 17 spinal cords from organ donors, aged between 37 and 83 years old. We examined the presence of ependymal cells using immunohistochemistry on lightly-fixed tissue. We found the presence of cells expressing the typical ependymal marker FOXJ1 in the spinal cord central region in 100% of cases. In addition, a lumen surrounded by FOXJ1+ cells was observed in half of the cases. Like in mice, these human ependymal cells maintain the expression of SOX2 and PAX6 proteins together with RFX2 a master transcriptional regulator of ciliogenesis and ARL13B, a regulatory GTPase enriched in cilia. Reminiscent of the situation observed in mice and in young human spinal cord, a fetal-like regionalization of neurodevelopmental transcription factors was observed in three donors aged over 75 years: MSX1 and ARX/FOXA2 was preferentially expressed by dorsal and ventral ependymal cells, respectively. These results provide new evidence for the persistence of ependymal cells expressing neurodevelopmental genes throughout human life. The persistence of these cells in humans opens new opportunities to regenerate the spinal cord.

show abstract

A Cellular Taxonomy of the Adult Human Spinal Cord

Cited by 14 publications

References 106 publications

Parvalbumin protein controls inhibitory tone in the spinal cord

Parvalbumin protein controls inhibitory tone in the spinal cord

Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics

Persistence of FoxJ1⁺ Pax6⁺ Sox2⁺ ependymal cells throughout life in the human spinal cord

Contact Info

Product

Resources

About

A Cellular Taxonomy of the Adult Human Spinal Cord

Cited by 14 publications

References 106 publications

Parvalbumin protein controls inhibitory tone in the spinal cord

Parvalbumin protein controls inhibitory tone in the spinal cord

Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics

Persistence of FoxJ1+ Pax6+ Sox2+ ependymal cells throughout life in the human spinal cord

Contact Info

Product

Resources

About

Persistence of FoxJ1⁺ Pax6⁺ Sox2⁺ ependymal cells throughout life in the human spinal cord