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Giacomini, D.

Publications and source records attributed to Giacomini, D..

3 recordsLinked to original sources

Cell-state mapping reveals a reversible neuroblast accumulation in the aging mouse hippocampus

Hippocampal neurogenesis supports learning and memory by generating new granule cells throughout life. However, both the rate and speed of this process decline with age. To elucidate the molecular determinants underlying the effects of aging on neuronal differentiation, we combined lineage tracing of adult-born granule cells (aGCs) with single-nucleus RNA sequencing. This approach produced a temporally resolved transcriptional atlas of aGC development. Aging led to a marked accumulation of postmitotic neuroblasts (NBs), revealing a stage-specific bottleneck in the neurogenic trajectory. Voluntary running reduced NB accumulation by restoring the progression through this developmental impasse, allowing neuronal maturation to be resumed. Notably, this effect involved a significant reduction of apoptosis at the NB stage. Together, these findings identify a reversible apoptotic checkpoint that contributes to age-related neurogenic decline and highlight postmitotic NBs as a key regulatory cell state capable of integrating pro-maturational signals to control the neurogenic output.

neuroscience↗

Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

The adult hippocampus generates new granule cells (aGCs) that exhibit distinct functional capabilities along development, conveying a unique form of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like neural stem cells (RGL) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to follow newborn aGCs along differentiation using single-nuclei RNA sequencing (snRNA-seq). Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple sequential immature stages bearing increasing levels of effector genes supporting growth, excitability and synaptogenesis. Remarkably, four discrete cellular states were defined by the expression of distinct sets of transcription factors (TFs): quiescent neural stem cells, proliferative progenitors, postmitotic immature aGCs, and mature aGCs. The transition from immature to mature aCGs involved a transcriptional switch that shutdown molecular cascades promoting cell growth, such as the SoxC family of TFs, to activate programs controlling neuronal homeostasis. Indeed, aGCs overexpressing Sox4 or Sox11 remained stalled at the immature state. Our results unveil precise molecular mechanisms driving adult neural stem cells through the pathway of neuronal differentiation.

neuroscience↗

Multiple modes of convergent adaptation in the spread of glyphosate-resistant Amaranthus tuberculatus

The selection pressure exerted by herbicides has led to the repeated evolution of herbicide resistance in weeds. The evolution of herbicide resistance on contemporary timescales in turn provides an outstanding opportunity to investigate key questions about the genetics of adaptation, in particular, the relative importance of adaptation from new mutations, standing genetic variation, or geographic spread of adaptive alleles through gene flow. Glyphosate-resistant Amaranthus tuberculatus poses one of the most significant threats to crop yields in the midwestern United States (1), with both agricultural populations and herbicide resistance only recently emerging in Canada (2, 3). To understand the evolutionary mechanisms driving the spread of resistance, we sequenced and assembled the A. tuberculatus genome and investigated the origins and population genomics of 163 resequenced glyphosate-resistant and susceptible individuals from Canada and the USA. In Canada, we discovered multiple modes of convergent evolution: in one locality, resistance appears to have evolved through introductions of preadapted US genotypes, while in another, there is evidence for the independent evolution of resistance on genomic backgrounds that are historically non-agricultural. Moreover, resistance on these local, non-agricultural backgrounds appears to have occurred predominantly through the partial sweep of a single haplotype. In contrast, resistant haplotypes arising from the midwestern US show multiple amplification haplotypes segregating both between and within populations. Therefore, while the remarkable species-wide diversity of A. tuberculatus has facilitated geographic parallel adaptation of glyphosate resistance, more recently established agricultural populations are limited to adaptation in a more mutation-limited framework.\n\nSignificanceWhile evolution is often thought of as playing out over millions of years, adaptation to new enviroments can occur in real time, presenting key opportunities to understand evolutionary processes. An important example comes from agriculture, where many weeds have evolved herbicide resistance. We have studied glyphosate resistant Amaranthus tuberculatus, a significant threat to crop yields in the midwestern US and Canada. Genome analyses showed that rapid evolution can either occur by \"borrowing\" resistance alleles from other locations, or by de novo evolution of herbicide resistance in a genetic background that was not previously associated with agriculture. Differences in recent evolutionary histories have thus favored either adaptation from pre-existing variation or new mutation in different parts of the A. tuberculatus range.

evolutionary biology↗