Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors—members of a “superarchaic” population that separated from other humans about 2 million years ago. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that (i) Denisovans also interbred with superarchaics, (ii) Neanderthals and Denisovans separated early in the middle Pleistocene, (iii) their ancestors endured a bottleneck of population size, and (iv) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (v) Neanderthals interbred with the ancestors of modern humans.

Highlights d Visceral fat contains subsets of stromal cells with distinct adipogenic potential d Cd34 high stromal cells inhibit adipogenesis through the secretion of soluble factors d Cd34 high stromal cells cause tissue remodeling and metabolic dysfunction in vivo

One-sentence summary We document the earliest known interbreeding between ancient human populations and an expansion out of Africa early in the middle Pleistocene.Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors-members of a "superarchaic" population that separated from other humans about 2 mya. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that: (1) Denisovans also interbred with superarchaics, (2) Neanderthals and Denisovans separated early in the middle Pleistocene, (3) their ancestors endured a bottleneck of population size, and (4) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (5) Neanderthals interbred with the ancestors of modern humans.

Objective Humans are unusually sexually dimorphic in body composition, with adult females having on average nearly twice the fat mass as males. The development of adipose sex differences has been well characterized for children growing up in food‐abundant environments, with less known about cross‐cultural variation, particularly in populations without exposure to market foods, mechanized technologies, schooling, vaccination, or other medical interventions. Methods To add to the existing cross‐cultural data, we fit multiple growth curves to body composition and anthropometric data to describe adipose development for the Savanna Pumé, South American hunter‐gatherers. Results (1) Little evidence is found for an adiposity ‘rebound’ at the end of early childhood among either Savanna Pumé girls or boys. (2) Rather, fat deposition fluctuates during childhood, from age ~4 to ~9 years, with no appreciable accumulation until the onset of puberty, a pattern also observed among Congo Baka hunter‐gatherers. (3) Body fat fluctuations are more pronounced for girls than boys. (4) The age of peak skeletal, weight, and adipose gains are staggered to a much greater extent among the Savanna Pumé compared to the National Health and Nutrition Examination Survey (NHANES III) reference, suggesting this is an important developmental strategy in lean populations. Conclusion Documenting growth patterns under diverse preindustrial energetic conditions provides an important baseline for understanding sex differences in body fat emerging today under food abundance.

Autocrine and paracrine signaling regulating adipogenesis in white adipose tissue remains largely unclear. Here we used single-cell RNA-sequencing (RNA-seq) and single nuclei RNA-sequencing (snRNA-seq) to identify markers of adipose progenitor cells (APCs) and adipogenic modulators in visceral adipose tissue (VAT) of humans and mice. Our study confirmed the presence of major cellular clusters in humans and mice and established important sex and diet-specific dissimilarities in cell proportions. Here we show that bone morphogenetic protein (BMP)-binding endothelial regulator (BMPER) is a conserved marker for APCs and adipocytes in VAT in humans and mice. Further, BMPER is highly enriched in lineage negative stromal vascular cells and its expression is significantly higher in visceral compared to subcutaneous APCs in mice. BMPER expression and release peaked by day four post-differentiation in 3T3-L1 preadipocytes. We reveal that BMPER is required for adipogenesis both in 3T3-L1 preadipocytes and in mouse APCs. Together, this study identified BMPER as a positive modulator of adipogenesis.