Cortical Neural Stem Cell Lineage Progression Is Regulated by Extrinsic Signaling Molecule Sonic Hedgehog.

Neural stem cells (NSCs) in the prenatal neocortex progressively generate different subtypes of glutamatergic projection neurons. Following that, NSCs have a major switch in their progenitor properties and produce γ-aminobutyric acid (GABAergic) interneurons for the olfactory bulb (OB), cortical oligodendrocytes, and astrocytes. Herein, we provide evidence for the molecular mechanism that underlies this switch in the state of neocortical NSCs. We show that, at around E16.5, mouse neocortical NSCs start to generate GSX2-expressing (GSX2+) intermediate progenitor cells (IPCs). In vivo lineage-tracing study revealed that GSX2+ IPC population gives rise not only to OB interneurons but also to cortical oligodendrocytes and astrocytes, suggesting that they are a tri-potential population. We demonstrated that Sonic hedgehog signaling is both necessary and sufficient for the generation of GSX2+ IPCs by reducing GLI3R protein levels. Using single-cell RNA sequencing, we identify the transcriptional profile of GSX2+ IPCs and the process of the lineage switch of cortical NSCs

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

Epigenetic Repression of RARRES1 Is Mediated by Methylation of a Proximal Promoter and a Loss of CTCF Binding

The cis-acting promoter element responsible for epigenetic silencing of retinoic acid receptor responder 1 (RARRES1) by methylation is unclear. Likewise, how aberrant methylation interplays effectors and thus affects breast neoplastic features remains largely unknown.We first compared methylation occurring at the sequences (-664~+420) flanking the RARRES1 promoter in primary breast carcinomas to that in adjacent benign tissues. Surprisingly, tumor cores displayed significantly elevated methylation occurring solely at the upstream region (-664~-86), while the downstream element (-85~+420) proximal to the transcriptional start site (+1) remained largely unchanged. Yet, hypermethylation at the former did not result in appreciable silencing effect. In contrast, the proximal sequence displayed full promoter activity and methylation of which remarkably silenced RARRES1 transcription. This phenomenon was recapitulated in breast cancer cell lines, in which methylation at the proximal region strikingly coincided with downregulation. We also discovered that CTCF occupancy was enriched at the unmethylayed promoter bound with transcription-active histone markings. Furthermore, knocking-down CTCF expression hampered RARRES1 expression, suggesting CTCF positively regulated RARRES1 transcription presumably by binding to unmethylated promoter poised at transcription-ready state. Moreover, RARRES1 restoration not only impeded cell invasion but also promoted death induced by chemotherapeutic agents, denoting its tumor suppressive effect. Its role of attenuating invasion agreed with data generated from clinical specimens revealing that RARRES1 was generally downregulated in metastatic lymph nodes compared to the tumor cores.This report delineated silencing of RARRES1 by hypermethylation is occurring at a proximal promoter element and is associated with a loss of binding to CTCF, an activator for RARRES1 expression. We also revealed the tumor suppressive roles exerted by RARRES1 in part by promoting breast epithelial cell death and by impeding cell invasion that is an important property for metastatic spread

The Overseeing Mother: Revisiting the Frontal-Pose Lady in the Wu Family Shrines in Second Century China

Located in present-day Jiaxiang in Shandong province, the Wu family shrines built during the second century in the Eastern Han dynasty (25–220) were among the best-known works in Chinese art history. Although for centuries scholars have exhaustively studied the pictorial programs, the frontal-pose female image situated on the second floor of the central pavilion carved at the rear wall of the shrines has remained a question. Beginning with the woman’s eyes, this article demonstrates that the image is more than a generic portrait (“hard motif ”), but rather represents “feminine overseeing from above” (“soft motif ”). This synthetic motif combines three different earlier motifs – the frontal-pose hostess enjoying entertainment, the elevated spectator, and the Queen Mother of the West. By creatively fusing the three motifs into one unity, the Jiaxiang artists lent to the frontal-pose lady a unique power: she not only dominated the center of the composition, but also, like a divine being, commanded a unified view of the surroundings on the lofty building, hence echoing the political reality of the empress mother’s “overseeing the court” in the second century during Eastern Han dynasty

Predicting the long-term fate of buried organic carbon in colluvial soils

A significant part of the soil organic carbon (SOC) that is eroded in uplands is deposited and buried in colluvial settings. Understanding the fate of this deposited soil organic carbon is of key importance for the understanding of the role of (accelerated) erosion in the global C cycle: the residence time of the deposited carbon will determine if, and for how long, accelerated erosion due to human disturbance will induce sequestration of SOC from the atmosphere to the soil. Experimental studies may provide useful information, but, given the time scale under consideration, the response of the colluvial SOC can only be simulated using numerical models which need careful calibration using field data. In this study, we present a depth explicit SOC model including soil profile evolution due to sedimentation to simulate the long-term C dynamics in colluvial soils. The SOC profile predicted by our model is in good agreement with field observations. The C burial efficiency (the ratio of current C content of the buried sediments to the original C content at the time of sedimentation) of deposited sediments exponentially decreases with time and gradually reaches an equilibrium value. This equilibrium C burial efficiency is positively correlated with the sedimentation rate. The sedimentation rate is crucial for the long-term dynamics of the deposited SOC as it controls the time that buried sediments spend at a given soil depth, thereby determining its temporal evolution of C input and decomposition rate during the burial process: C input and decomposition rate vary with depth due to the vertical variation of root distribution and soil environmental factors such as (but not limited to) humidity, temperature, and aeration. The model demonstrates that, for the profiles studied, it takes circa 300 years for the buried SOC to lose half of its C load. It would also take centuries for the SOC accumulated in colluvial soils over the past decades due to soil redistribution under mechanized agriculture to be released to the atmosphere after the application of soil conservation measures such as conservation tillage

Timing the Carbon Cycle: how far does the Soil Erosion Benefit Stretch?

Several papers have now convincingly shown that, on the short term, the intensification of soil erosion due to human activities does not lead to a massive emission of soil organic carbon. Rather, agricultural soil erosion may be responsible for a relatively small carbon sink. This conclusion is mainly based on the fact that a large fraction of the eroded carbon is dynamically replaced by additional soil carbon uptake at eroding sites and the behaviour of the carbon stores created by deposition. Over decadal time periods a large amount of the deposited carbon is indeed retained within the soil reservoir, thereby leading to net extra carbon storage. It is still unclear, however, how stable such stores are over longer time spans. We therefore sampled both active and historical colluvial depositional stores in different landscape settings in the Loess Belt of central Belgium. We determined the total amount of carbon stored as well as the variation in its stable isotope composition and a limited number of samples were subjected to incubation runs. The age of the deposits was determined as accurately as possible by measuring total phosphorous as well as 137Cs analysis as well as by interpreting historical maps and aerial photographs. We used our data to calibrate and validate a simple soil carbon model using two carbon pools only. While the values of the calibration parameters that we obtained for our different sites varied, the results with respect to the lifespan of a soil carbon store created by deposition were consistent. Model simulations show that, under realistic conditions, depositional carbon stores reach equilibrium after 300-1500 years, depending on the deposition rate. At this stage, 20 to 50 % of the deposited soil organic carbon is still present in the colluvium. When accounting for the effects of soil erosion on the global carbon cycle it is therefore important to consider the dynamics of depositional stores over longer time spans. Our analysis shows that the significant carbon losses from these stores must be accounted for when considering long-term effects of agricultural soil erosion on the global carbon cycle

The fate of buried organic carbon in colluvial soils: a long-term perspective

Colluvial soils are enriched in soil organic car- bon (SOC) in comparison to the soils of upslope areas due to the deposition and progressive burial of SOC. This burial of SOC has important implications for the global carbon cycle, but the long-term dynamics of buried SOC remain poorly constrained. We addressed this issue by determining the SOC burial efficiency (i.e. the fraction of originally de- posited SOC that is preserved in colluvial deposits) of buried SOC as well as the SOC stability in colluvial soils. We quan- tified the turnover rate of deposited SOC by establishing sed- iment and SOC burial chronologies. The SOC stability was derived from soil incubation experiments and the δ 13 C val- ues of SOC. The C burial efficiency was found to decrease with time, reaching a constant ratio of approximately 17 % by about 1000–1500 yr post-burial. This decrease is attributed to the increasing recalcitrance of the remaining buried SOC with time and a less favourable environment for SOC decom- position with increasing depth. Buried SOC in colluvial pro- files was found to be more stable and degraded in compari- son to SOC sampled at the same depth at a stable reference location. This is due to the preferential mineralisation of the labile fraction of the deposited SOC. Our study shows that SOC responds to burial over a centennial timescale; how- ever, more insight into the factors controlling this response is required to fully understand how this timescale may vary, depending on specific conditions such as climate and depo- sitional environment