Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG , encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with EPIREGULIN promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. EPIREGULIN competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of EPIREGULIN expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone.

Background/Objectives: Hartmann’s procedure is commonly employed to manage complications of acute sigmoid diverticulitis, such as perforation or abscess formation. However, determining the optimal timing for colostomy reversal remains a topic of debate. This study aims to evaluate the effect of early versus delayed colostomy reversal on postoperative outcomes, focusing on complications, hospital stay duration, and readmission rates. Methods: A retrospective cohort study was conducted on 148 patients who underwent Hartmann’s procedure for acute sigmoid diverticulitis at a single tertiary care center between 2014 and 2023. Participants were grouped based on the timing of colostomy reversal: early (45–120 days), intermediate (121–180 days), and late (>180 days). Data on complications, hospital stay length, and readmissions were analyzed. Results: Early reversal was associated with fewer postoperative complications, shorter hospital stays, and reduced readmissions compared to delayed reversal. The late reversal group had higher rates of complications, longer hospital stays, and a higher need for reintervention. Advanced age and comorbidities, such as cardiovascular disease and diabetes, were significant predictors of poor outcomes, contributing to delayed reversal. Logistic regression analysis indicated that late reversal was independently associated with higher complication rates. Conclusions: Early colostomy reversal within 45–120 days following Hartmann’s procedure is associated with improved postoperative outcomes, including fewer complications and a shorter hospital stay. The timing of colostomy reversal should be individualized based on patient health status, with early reversal preferred for those without significant comorbidities. Further prospective research is needed to confirm these findings and refine guidelines for optimal reversal timing.

Summary: Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodelling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass cytometry-based approach for the simultaneous single cell analysis of more than 30 epigenetic marks. We identify H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), as the modification with the strongest cell type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation towards differentiation. Cell type- specific profiling of H3K27me3 not only identified neuronal differentiation genes in the human neocortex, but also extra-cellular matrix (ECM) genes. PRC2 inhibition resulted in increased production of the proteoglycan Syndecan 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.