Single-cell delineation of lineage and genetic identity in the mouse brain

Abstract

During neurogenesis, mitotic progenitor cells lining the ventricles of the embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia1,2. The link between developmental lineage and cell-type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during mouse forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neuron that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent process at the progenitor cell level.

Combined single-cell RNA-seq profiling and enhancer editing reveals critical spatiotemporal controls over thalamic nuclei formation in the murine embryo

“…9). Although these results are based on the continuity of gene expression programs across cell differentiation and cannot be relied upon to define clonal relationships, they are consistent with recent clonal studies of the mouse forebrain showing a common progenitor origin for GABAergic neurons with drastically different transcriptomic profiles and anatomical locations 54 . We conclude that GABAergic neurons of the thalamus derive from Tal1 + neural progenitors and are characterized by the expression of Shh-responsive genes.…”

An epigenome atlas of neural progenitors within the embryonic mouse forebrain

“…Both APs and BPs give rise to postmitotic immature neurons (Ns) within the GEs that migrate tangentially to populate the telencephalon. Recent evidence demonstrates that initial interneuron subtype fate is specified within the GEs as interneuron progenitors exit the cell cycle [8][9][10][11] . It is well established that changes in a cell's epigenetic landscape alters cell fate decisions throughout normal development 12,13 and can be associated with neurodevelopmental disorders [14][15][16] .…”

Fast model-free standardization and integration of single-cell transcriptomics data

“…Next, we utilized these cell-type features to integrate multi-batch temporal scRNA-Seq datasets for lineage analysis. For this, we selected three datasets for lineage analysis: 1) human peripheral blood mononuclear cell (PBMC) data of patients with Kawasaki disease obtained before and after IVIG (intravenous immunoglobulin) treatment 38 , 2) mouse brain lineage tracing at different time points 39 , and 3) zebrafish embryo from two studies that cover 13 major developmental stages 40,41 .…”

“…Both human hematopoiesis and mouse brain lineage tracing studies were in multi-condition design, and we were able to obtain cell-type markers from an externally annotated 10X Genomics PBMC data 30 , while author-verified cell-type markers from the original report were used for the mouse brain lineage tracking study 39 . We constructed an integrative lineage map with cell-type score matrices and visualized population density and cell-type score (Fig.…”