Welling, M. | bioRxiv Science

bioRxiv2026

The south Congo Basin was critical to Bantu settlement of south central Africa

South central Africa, between the Congo Basin, the Great Lakes, and southern Africa, has long served as a corridor for human movement. Yet, it remains unclear whether there is genetic continuity between pre-Iron Age foragers and later Bantu-associated populations and whether the settlement of this region reflects multiple Bantu-associated migrations rather than the simpler serial founder model suggested by existing genomic data. To do so, we generated genome-wide ancient DNA from 71 Iron Age and historical individuals from present-day Zambia and Malawi, and analyzed these genomes alongside published data from present-day Africans. One late Iron Age individual (16th-17th century) from Kalala Island in the Kafue River, Zambia, carries 40% non Bantu related ancestry that closely matches local Later Stone Age foragers. Admixture for this individual is estimated to be 850 years ago, several centuries earlier than reported for present day BaTwa from the same region. Focusing on the Bantu-related ancestry, haplotype-based analyses identify two main clusters among Iron Age, historical, and present-day south central Bantu groups associated with different Bantu-related migrations. These results reveal a layered history in which at least two Bantu expansions radiated from the southern Congo Basin, with south central Africa acting both as a crossroads of these movements and as a staging area for the subsequent southward expansion toward southern Africa.

evolutionary biology↗

bioRxiv2020

The helminth glycoprotein omega-1 improves metabolic homeostasis in obese mice through type-2 immunity-independent inhibition of food intake

Type 2 immunity plays an essential role in the maintenance of metabolic homeostasis and its disruption during obesity promotes meta-inflammation and insulin resistance. Infection with the helminth parasite Schistosoma mansoni and treatment with its soluble egg antigens (SEA) can induce a type 2 immune response in metabolic organs and improve insulin sensitivity and glucose tolerance in obese mice, yet a causal relationship remains unproven. Here, we investigated the effects and underlying mechanisms of the T2 ribonuclease omega-1 (ω1), one of the major S. mansoni immunomodulatory glycoproteins, on metabolic homeostasis. Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by bi-weekly injection of SEA, ω1 or vehicle for 4 additional weeks. Whole-body metabolic homeostasis and energy expenditure were assessed by glucose/insulin tolerance tests and indirect calorimetry, respectively. Tissue-specific immune cell phenotypes were determined by flow cytometry. We show that treatment of obese mice with plant-produced recombinant ω1, harboring similar glycan motifs as present on the native molecule, decreased body fat mass and improved systemic insulin sensitivity and glucose tolerance in a time-and dose-dependent manner. This effect was associated with an increase in white adipose tissue (WAT) type 2 T helper cells, eosinophils and alternatively-activated macrophages, without affecting type 2 innate lymphoid cells. In contrast to SEA, the metabolic effects of ω1 were still observed in obese STAT6-deficient mice with impaired type 2 immunity, indicating that its metabolic effects are independent of the type 2 immune response. Instead, we found that ω1 inhibited food intake, without affecting locomotor activity, WAT thermogenic capacity or whole-body energy expenditure, an effect also occurring in leptin receptor-deficient obese and hyperphagic db/db mice. Altogether, we demonstrate that while the helminth glycoprotein ω1 can induce type 2 immunity, it improves whole-body metabolic homeostasis in obese mice by inhibiting food intake via a STAT6-independent mechanism.Author summary The obesity-induced chronic low-grade inflammation, notably in adipose tissue, contributes to insulin resistance and increased risk of type 2 diabetes. We have previously shown that infection with parasitic helminth worms was associated with protection against obesity-related metabolic dysfunctions both in mice and humans. We have also reported that treatment of obese mice with an extract of Schistosoma mansoni eggs (SEA) improves insulin sensitivity and glucose tolerance, a beneficial effect that was associated with a helminth-specific type 2 immune response in metabolic organs. Here, we studied the effects of omega-1 (ω1), a single immunomodulatory molecule from SEA, on metabolic health in obese mice, and investigated the role of the host immune response elicited. We found that ω1 induced a helminth-characteristic type 2 immune response in adipose tissue and improved both insulin sensitivity and glucose tolerance in obese mice. Yet, in contrast to SEA, ω1’s immunomodulatory properties were dispensable for its metabolic effects. Instead, we show that ω1 inhibited food intake, a feature accounting for most of the improvements in metabolic health. Together, our findings indicate that helminth molecules may improve metabolic health through multiple distinct mechanisms, and further characterization of such molecules could lead to new therapeutic strategies to combat obesity.List of abbreviationsAAMAlternatively activated macrophageALATAlanine aminotransferaseBATBrown adipose tissueDCDendritic cellEEEnergy expenditureGTTGlucose tolerance testHEKHuman embryonic kidneyHFDHigh-fat dietHOMA-IRHomeostatic model assessment of insulin resistanceIFN-γInterferon gammaILInterleukinILCInnate lymphoid cellITTInsulin tolerance testLBMLean body massLFDLow-fat dietNAFLDNon-alcoholic fatty liver diseaseNASHNon-alcoholic steatohepatitispLeX-ω1Recombinant omega-1 from LeX-glyco-engineered Nicotiana benthamiana plantsPMAPhorbol myristate acetatepWT-ω1Recombinant omega-1 from wild-type N. benthamiana plantsSEASchistosoma mansoni soluble egg antigensSTATSignal transducer and activator of transcriptionSVFStromal vascular fractionThT helperTNFTumor necrosis factorUCP1Uncoupling protein 1WATWhite adipose tissueWTWild-typeView Full Text

immunology↗

bioRxiv2019

GenEPi: Piezo1-based fluorescent reporter for visualizing mechanical stimuli with high spatiotemporal resolution

Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses during development, homeostasis, and disease. However, non-invasive investigation of cellular mechanosensing in complex and intact live tissue remains challenging. Here, we developed GenEPi, a genetically-encoded fluorescent intensiometric reporter for mechanical stimuli based on Piezo1, an essential mechanosensitive ion channel found in vertebrates. We show that GenEPi has high specificity and spatiotemporal resolution for Piezo1-dependent mechanical stimuli, exemplified by resolving repetitive mechanical stimuli of spontaneously contracting cardiomyocytes within microtissues, in a non-invasive manner.

cell biology↗

bioRxiv2017

High fidelity lineage tracing in mouse pre-implantation embryos using primed conversion of photoconvertible proteins

Accurate lineage reconstruction of mammalian pre-implantation development is essential for inferring the earliest cell fate decisions of mammalian development. Lineage tracing using global labeling techniques is complicated by increasing cell density and rapid embryo rotation, impeding automatic alignment and rendering accurate cell tracking of obtained four-dimensional imaging data sets highly challenging. Here, we exploit the advantageous properties of primed convertible fluorescent proteins (pr-pcFPs) to simultaneously visualize the global green and the photoconverted red population to minimize tracking uncertainties over prolonged time windows. Confined primed conversion of H2B-pr-mEosFP labeled nuclei combined with light-sheet imaging greatly facilitates segmentation, classification, and tracking of individual nuclei from the 4-cell stage up to the blastocyst. Using green and red labels as fiducial markers, we computationally correct for rotational and translational drift and accomplish high fidelity lineage tracing combined with a reduced data size - addressing majors concerns in the field of volumetric embryo imaging.

developmental biology↗