Dataset Information

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

ABSTRACT: The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

SUBMITTER: Paredes MF

PROVIDER: S-EPMC8887556 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

Paredes Mercedes F MF Mora Cristina C Flores-Ramirez Quetzal Q Cebrian-Silla Arantxa A Del Dosso Ashley A Larimer Phil P Chen Jiapei J Kang Gugene G Gonzalez Granero Susana S Garcia Eric E Chu Julia J Delgado Ryan R Cotter Jennifer A JA Tang Vivian V Spatazza Julien J Obernier Kirsten K Ferrer Lozano Jaime J Vento Maximo M Scott Julia J Studholme Colin C Nowakowski Tomasz J TJ Kriegstein Arnold R AR Oldham Michael C MC Hasenstaub Andrea A Garcia-Verdugo Jose Manuel JM Alvarez-Buylla Arturo A Huang Eric J EJ

Science (New York, N.Y.) 20220128 6579

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mous ...[more]

PMID: 35084970

Similar Datasets

Project description:The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4(+) CD45RA(-) CD25(-) CCR6(+) Th17 cells, primary human VIC were cultured in vitro and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4(+) T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify the release of neutrophilic contents in situ, which might lead to severe valvular damage.

Dataset Information

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

Publications

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets