Mount Sinai Researchers Present a Comprehensive, Single-nucleus RNA Sequencing Atlas of Late Prenatal Human Development

MEDIA ADVISORY  

FOR IMMEDIATE RELEASE: Nature Communications December 12, 2022

Corresponding Author:  Nadejda Tsankova, MD, PhD, Associate Professor of Pathology and Neuroscience, Director of Neuropathology, Icahn School of Medicine at Mount Sinai

Bottom Line: This human transcriptomics study uniquely captures the transience, diversity and lineage choice of cells as the brain grows in middle and late prenatal development, including novel glial progenitor signatures with relevance to disease.

Why the Research Is Interesting:  Late prenatal development of the human neocortex encompasses a critical period of cortical expansion and glial development (cells that are essential to the central nervous system), which is poorly understood, in part due to limited availability of tissue samples from this period. In this study, the research team performed high-throughput computational analysis to resolve, for the first time, the entire human glial lineage trajectory during the second and third trimesters of brain development.

Who:  15 prenatal, non-pathological postmortem samples from 17 to 41 gestational weeks, and 3 adult controls

When: Late prenatal human brain development

What:  Transcriptomic analysis

How:  Single cell transcriptomic analysis of cell type diversity and lineage choice, followed by validation in primary human autopsy tissue 

Study Conclusions: Computational analysis uncovers a greater complexity of glial progenitors, including transient glial intermediate progenitor cell (gIPC) and nascent astrocyte populations in the third trimester of human gestation. The research team demonstrate enrichment of specific prenatal glial cell-type signatures in several disease states, including intellectual disability, autism spectrum disorder, malformation of cortical development, and gliomas.

Paper Title: An atlas of late prenatal human neurodevelopment resolved by singles-nucleus transcriptomics

Said Mount Sinai's Dr. Tsankova of the research:
“Late prenatal development of the human neocortex encompasses a critical period of cortical expansion and glial development, which is poorly understood, in part due to limited availability of tissue samples from this period. Working together, our team of pathologists, neurodevelopmental biologists, and computational biologists generated a high-throughput atlas of late prenatal human brain development, examining both the niche where stem cells are born and the niche where maturing progenitors migrate to. This atlas uniquely captures both the transience and the diversity of glial and neuronal progenitors during late prenatal growth. Importantly, our study resolves a specific glial progenitor population, gIPC, common to both oligodendrocyte and astrocyte lineages. We also demonstrate the enrichment of newly discovered prenatal glial signatures in several disease states, including intellectual disability, autism spectrum disorder, malformation of cortical development, and gliomas. Beyond this study, our resource dataset motivates further interrogation into both normal human development and clinical association to disease.”  

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