Biology subjects

Spangenberg, L.

Publications and source records attributed to Spangenberg, L..

6 recordsLinked to original sources

bioRxiv2026

Genetic and Behavioral Variation Underlying an Integrated Temporal Phenotype in an Admixed South American Population

Chronotype is a complex trait reflecting individual differences in the temporal organization of rest and activity, with important health implications. The Uruguayan population, characterized by a tri-hybrid origin (African, European, and Indigenous), exhibits a bias toward eveningness. The genetic variation in clock genes underlying chronotype in this population remains unexplored. To address this gap, we analyze healthy young adults from the extremes of the chronotype distribution (early, n = 37; late, n = 38; 63% female; 23.1 {+/-} 3.4 years), integrating self-reported measures, actigraphy, and low-pass whole-genome sequencing. Global ancestry is predominantly European, with Indigenous and African components, and does not differ between chronotypes. Variant density is highest in PER2. T-allele carriers of a PER2 variant previously associated with late chronotypes (rs35333999) differ from non-carriers in activity acrophase. Multidimensional scaling of variants across 19 canonical clock genes reveal differential representation of early and late chronotypes across genetic clusters. When examined by functional groups, the signal is restricted to genes involved in degradation of the circadian clock's repressor arm, with BTRC, a mediator of PER2 degradation, showing the same pattern when assessed individually. We derive a joint behavioral component capturing the variation in food intake, moderate-to-vigorous physical activity, light exposure, and sleep timing, which correlates with dim-light melatonin onset (DLMO), the gold-standard marker of circadian phase, and show differences among genetic clusters. Our integrative multilevel approach suggests a complex interplay between behavioral and genetic factors shaping chronotype in this cohort, highlighting the PER2BTRC axis as a candidate mechanism for future investigations.

genetics↗

bioRxiv2026

CSDC2, an RBP essential to cardiomyocyte commitment during cardiac differentiation in hiPSC

Cardiovascular diseases are the leading cause of death worldwide, accounting for approximately 30% of total mortality. Changes in post-transcriptional regulation have been correlated with the development of cardiopathies. RNA-binding proteins (RBP) are proteins capable of interacting with mRNAs, regulating their stability, localization, and translation. Here, we described CSDC2 as an RBP expressed at the final stages of cardiac differentiation using hPSCs as a model. We showed that the loss of CSDC2 impairs cardiomyocyte differentiation, while the recovery of its expression rescues the differentiation potential of these cells. We characterized the translatome of CSDC2 knockout cells during cardiac differentiation by polysome profiling. In cardiac mesoderm cells, CSDC2 interacts with ribosomal proteins. Furthermore, CSDC2 appears to be able to associate with mRNAs encoding regulators of cardiac progenitor commitment. Altogether, in this study, we describe a new role of CSDC2 in cardiomyocyte commitment using cardiac differentiation of hiPSCs.

molecular biology↗

bioRxiv2025

The shared genomic history of Middle to Late Holocene Southern Cone populations

The Southern Cone represents the southernmost region of South America to be colonized by humans. Although ancient genomes have been sequenced from southern Patagonia, genomic data from the central Southern Cone remain temporally and spatially sparse. The archaeological record of this region documents major cultural transformations during the Middle and Late Holocene, yet their relationship to demographic processes has long been debated. Here, we present genome-wide data from 52 individuals spanning the past 5,000 years, originating from four regions of the central Southern Cone in present-day Argentina and Uruguay: the central and southern Pampas, Northwest Patagonia, the Parana River Delta and Lower Uruguay River, and the eastern lowlands of Uruguay. Genomic evidence from the Pampas reveals the presence of at least three distinct ancestries during the Middle Holocene. While genetic contacts with southern Patagonian groups were sporadic, we identify the expansion of an ancestry of unknown geographic origin by 4,800 years ago, which increased substantially during the Late Holocene. This same ancestry arrived in Northwest Patagonia by at least 600 years ago, and it co-existed with individuals carrying a southern Andean genetic profile until colonial times. Genetic structure differentiates populations along the Parana River Delta and the Lower Uruguay River by approximately 1,600 years ago. In contrast, individuals from the eastern lowlands of Uruguay show genetic links with Sambaqui-associated populations from the southern coast of Brazil, suggesting the role of human dispersals in connecting tropical lowland cultural traditions. Overall, our work documents the diffusion of genetically distinct groups across all regions studied and provides compelling evidence that large-scale human movements contributed to the remarkable cultural diversity of central Southern Cone populations during the Middle and Late Holocene.

genetics↗

bioRxiv2025

SiteCELL enables on-site PBMCs purification and cryopreservation for immune single cell profiling of diverse ancestries

Single cell genomics has improved our knowledge of immune function and heterogeneity. In recent years, the steady increase in the number of cells and individuals profiled as part of large multinational projects has enabled the characterization of cellular differences across human populations and ancestries. However, methods for collecting and processing peripheral blood mononuclear cells (PBMCs) for downstream single cell sequencing are difficult to implement in remote and rural settings. This has resulted in a lack of representation of underserved communities across the Global South in current initiatives. Hence, we developed SiteCELL, a method that enables purification and cryopreservation of PBMCs from whole blood at the site of collection using minimal laboratory equipment and without electricity. By comparing matched samples of purified PBMCs, we showed that SiteCELL performs as well as ficoll density gradient (FDG), both in laboratory and rural settings. This method ensures accurate recovery of cell type proportions and excels in reducing stress and minimizing variability across sampling batches. These advantages make it particularly well suited for implementation in challenging settings across countries, thereby enabling the inclusion of underrepresented ancestries in cellular atlases.

immunology↗

bioRxiv2021

Indigenous ancestry and admixture in the Uruguayan population

The Amerindian group known as the Charruas inhabited Uruguay at the timing of European colonial contact. Even though they were extinguished as an ethnic group as a result of a genocide, Charruan heritage is part of the Uruguayan identity both culturally and genetically. While mitochondrial DNA studies have shown evidence of Amerindian ancestry in living Uruguayans, here we undertake whole-genome sequencing of 10 Uruguayan individuals with Charruan heritage. We detect chromosomal segments of Amerindian ancestry supporting the presence of indigenous genetic ancestry in living descendants. Specific haplotypes were found to be enriched in Charruas and rare in the rest of the Amerindian groups studied. Some of these we interpret as the result of positive selection, as we identified selection signatures and they were located mostly within genes related to the infectivity of specific viruses. Historical records describe contacts of the Charruas with other Amerindians, such as Guarani, and patterns of genomic similarity observed here concur with genomic similarity between these groups. Less expected, we found a high genomic similarity of the Charruas to Diaguita from Argentinian and Chile, which could be explained by geographically proximity. Finally, by fitting admixture models of Amerindian and European ancestry for the Uruguayan population, we were able to estimate the timing of the first pulse of admixture between European and Uruguayan indigenous peoples in 1658 and the second migration pulse in 1683. Both dates roughly concurring with the Franciscan missions in 1662 and the foundation of the city of Colonia in 1680 by the Spanish.

genomics↗

bioRxiv2019

FUNCTION OF PUMILIO GENES IN HUMAN EMBRYONIC STEM CELLS AND THEIR EFFECT IN STEMNESS AND CARDIOMYOGENESIS

Posttranscriptional regulation plays a fundamental role in the biology of embryonic stem cells (ESCs). Many studies have demonstrated that multiple mRNAs are coregulated by one or more RNA binding proteins (RBPs) that orchestrate the expression of these molecules. A family of RBPs, known as PUF (Pumilio-FBF), is highly conserved among species and has been associated with the undifferentiated and differentiated states of different cell lines. In humans, two homologs of the PUF family have been found: Pumilio 1 (PUM1) and Pumilio 2 (PUM2). To understand the role of these proteins in human ESCs (hESCs), we first demonstrated the influence of the silencing of PUM1 and PUM2 on pluripotency genes. OCT4 and NANOG mRNA levels decreased significantly with the knockdown of Pumilio, suggesting that PUMILIO proteins play a role in the maintenance of pluripotency in hESCs. Furthermore, we observed that the hESCs silenced for PUM1 and 2 exhibited an improvement in efficiency of in vitro cardiomyogenic differentiation. Using in silico analysis, we identified mRNA targets of PUM1 and PUM2 expressed during cardiomyogenesis. With the reduction of PUM1 and 2, these target mRNAs would be active and could be involved in the progression of cardiomyogenesis.

molecular biology↗