Regional differences in enterocyte function across development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1284787 | ENA |
REPOSITORIES: ENA
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Project description:Mammalian brain development is characterized by disproportionate forebrain expansion, yet the mechanisms underlying this regional growth specificity remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbrain neurogenesis is transient and restricted to early development, forebrain neurogenesis is temporally sustained through reduced consumptive divisions of ventricular zone progenitors, maintaining its germinal pool. This atlas additionally reveals region-specific patterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarily conserved cell-cycle programs and metabolism-related molecular pathways that control regional temporal windows of proliferation. We identify the late forebrain-enriched mitochondrial protein Fam210b as a key regulator using in vivo gain- and loss-of-function experiments. Fam210b elongates mitochondria and increases lactate production, which promotes progenitor self-renewing divisions and, ultimately, larger clonal size of their progeny. Together, these findings indicate spatiotemporal heterogeneity in mitochondrial function regulates progenitor cycling behavior and regional neuronal production during brain development.
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Project description:Mammalian brain development is characterized by disproportionate forebrain expansion, yet the mechanisms underlying this regional growth specificity remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbrain neurogenesis is transient and restricted to early development, forebrain neurogenesis is temporally sustained through reduced consumptive divisions of ventricular zone progenitors, maintaining its germinal pool. This atlas additionally reveals region-specific patterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarily conserved cell-cycle programs and metabolism-related molecular pathways that control regional temporal windows of proliferation. We identify the late forebrain-enriched mitochondrial protein Fam210b as a key regulator using in vivo gain- and loss-of-function experiments. Fam210b elongates mitochondria and increases lactate production, which promotes progenitor self-renewing divisions and, ultimately, larger clonal size of their progeny. Together, these findings indicate spatiotemporal heterogeneity in mitochondrial function regulates progenitor cycling behavior and regional neuronal production during brain development.
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Project description:Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed. Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples. Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization.
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