Early Forebrain Neurons and Scaffold Fibers in Human Embryos

Qin, Jingwen; Wang, Meizhi; Zhao, Tianyun; Xiao, Xue; Li, Xuejun; Yang, Jieping; Yi, Lingling; Goffinet, André M.; Qu, Yibo; Zhou, Libing

doi:10.1093/cercor/bhz136

Cited by 10 publications

(12 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Newborn neurons marked by DCX were identifiable as early as CS14, but markers of maturing neuronal identity such as BCL11B (CTIP2) emerged after CS16. As expected, IPCs identified by TBR2 staining did not emerge until CS18 in the dorsal telencephalon 26 (Fig 1B, SFig 13), though we and others have observed TBR2 staining at earlier timepoints (CS16) in the ventral telencephalon 27 .…”

Section: Resultssupporting

confidence: 85%

Single-Cell Atlas of Early Human Brain Development Highlights Heterogeneity of Human Neuroepithelial Cells and Early Radial Glia

Eze

Bhaduri

Nowakowski³

et al. 2020

Preprint

View full text Add to dashboard Cite

The human cortex is comprised of diverse cell types that emerge from an initially uniform neuroepithelium that, following neural tube closure, gives rise to radial glia, the neural stem cells of the cortex. Radial glia initially reside in the ventricular zone of the cortex, and contribute to cortical expansion which is particularly pronounced in the human compared to other mammals and non-human primates. To characterize the molecular signatures of cellular subtypes that may exist at the earliest stages of neurogenesis we performed single-cell RNA-sequencing across regions of the developing human brain. We observe similar progenitor programs across brain regions that each express region-specific transcription factors. In the telencephalon, we identify nine progenitor populations, suggesting more heterogeneity among neuroepithelial cells and radial glia than previously described, including a highly prevalent mesenchymal-like population that disappears after the onset of neurogenesis. Using velocity analysis, we find that genes implicated in various neurodevelopmental diseases drive the specification and maintenance of neuroepithelial cells and radial glia. Comparison of these progenitor populations to corresponding stages of mouse development identifies two progenitor clusters that are unique to the early stages of human cortical development. Organoid systems display a low fidelity to neuroepithelial and early radial glia cell types, but this improves as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.The human brain consists of billions of cells across several functionally interconnected structures that emerge from the neuroectoderm. Many of these structures are substantially expanded or distinct compared to other mammals 1 , particularly the cerebral cortex, the outermost layer of the human brain responsible for perception and cognition. These differences emerge at developmental stages prior to birth 2 , and thus exploring the cell types in the developing human brain is essential to better characterize how cell types across the brain are generated, how they may be impacted during the emergence of neurodevelopmental disorders, and how human neural stem cells can be directed to specific cell types for modeling or treatment purposes. The brain exponentially increases in size after the neural tube closes 3,4 . Later in development, across brain regions, a series of similar neurogenic and gliogenic processes gives rise to the constituent cell types 5 . However, at the molecular level, the sequence of events that leads to the emergence of these progenitor cells early in development is much less well understood. In order to identify cell types and trajectories that lay the foundation for the development of the human brain, we performed single-cell RNA sequencing (scRNA-seq) using the droplet-based 10X Genomics Chromium platform on ten individuals during the first trimester of human development, spanning Carnegie Stages (CS) ...

show abstract

Section: Resultssupporting

confidence: 85%

Single-Cell Atlas of Early Human Brain Development Highlights Heterogeneity of Human Neuroepithelial Cells and Early Radial Glia

Eze

Bhaduri

Nowakowski³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…1A, D). PAX6 expression was confined to the dorsal telencephalon where the protein was detected in apical radial glial cells (aRGCs) in the VZ and in a few progenitors in the SVZ with a lateral high to medial low expression gradient (Fig, 1B, E) as described previously (Clowry et al, 2018; Qin et al, 2020). Moreover, cortical projection neurons residing in the forming cortical plate were identified by the expression of TBR1 (Fig.…”

Section: Resultssupporting

confidence: 67%

The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling

Schembs

Willems

Hasenpusch‐Theil

et al. 2021

Preprint

View full text Add to dashboard Cite

Defects in primary cilia, cellular antennas that controls multiple intracellular signalling pathways, underlie several neurodevelopmental disorders, but how cilia control essential steps in human brain formation remains elusive. Here, we show that cilia are present on the apical surface of radial glial cells in human foetal forebrain. Interfering with cilia signalling in human organoids by mutating the INPP5E gene leads to the formation of ventral telencephalic cell types instead of cortical progenitors and neurons. INPP5E mutant organoids also showed increased SHH signalling and cyclopamine treatment partially rescued this ventralisation. In addition, ciliary expression of SMO was increased and the integrity of the transition zone was compromised. Overall, these findings establish the importance of primary cilia for dorsal/ventral patterning in human corticogenesis, indicate a tissue specific role of INPP5E as a negative regulator of SHH signalling and have implications for the emerging roles of cilia in the pathogenesis of neurodevelopmental disorders.

show abstract

“…1b and Supplementary Fig. 13), although we and others have observed TBR2 staining at earlier timepoints (CS16) in the ventral telencephalon 27 .…”

Section: Nature Neurosciencementioning

confidence: 48%

Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

et al. 2021

View full text Add to dashboard Cite

The human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

show abstract

Early Forebrain Neurons and Scaffold Fibers in Human Embryos

Cited by 10 publications

References 91 publications

Single-Cell Atlas of Early Human Brain Development Highlights Heterogeneity of Human Neuroepithelial Cells and Early Radial Glia

Single-Cell Atlas of Early Human Brain Development Highlights Heterogeneity of Human Neuroepithelial Cells and Early Radial Glia

The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling

Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

Contact Info

Product

Resources

About