Researchers trace brown fat to an unexpected embryonic source at the aorta

A team of scientists has identified an unexpected embryonic “starting point” for several brown-fat depots: a small cell niche around the dorsal aorta. Using a combination of time-controlled genetic lineage tracing and single-cell RNA sequencing in early mouse embryos, the researchers show that progenitor cells from this aorta-adjacent region later contribute to brown fat in multiple body locations—while the best-known depot between the shoulder blades (interscapular region) is only minimally derived from this source. The study is published in Nature Communications.

Brown adipose tissue—often called “brown fat”—helps mammals regulate their body temperature, and it is drawing growing attention as obesity rises worldwide. Brown fat is not uniform across the body, however; it appears in distinct anatomical depots, and these depots differ in cellular composition and gene activity. Researchers often use one depot as a model for “brown fat” in general, but if depots do not share the same developmental origin, they may also differ in how they are regulated—and in how reliably findings from one region translate to another.

“Previous studies suggested that brown fat depots might not all develop in the same way,” says Prof. Sigmar Stricker, Head of the Department of Cell Biology at KL Krems. “We have now used lineage tracing and single-cell data to check this idea in more detail—and, indeed, we found strong evidence for a yet unknown location of progenitor cells of brown adipose tissue near the dorsal aorta.”

The team around Prof. Stricker focused on cells expressing the gene Osr1 (a transcription factor) and followed the development and migration of these cells over time. By labeling Osr1-positive cells at defined embryonic stages, they uncovered clear depot-specific patterns: Osr1-lineage cells contributed strongly to brown fat beneath the shoulder blade (subscapular) and in the neck (cervical) regions, but only minimally to the large depot between the shoulder blades (interscapular)—a widely used reference tissue in mouse studies.

An even earlier labeling time point still revealed substantial contributions to the subscapular and cervical depots, indicating that relevant Osr1-positive progenitors are present very early in development.

Single-cell RNA sequencing added the molecular context. At a later embryonic stage, Osr1-positive cells showed a clearer “pre–brown fat” signature. At an earlier stage, however, a subset displayed a broader, multipotent profile, with gene-expression features linked to vascular- and muscle-related programs. Consistent with this, lineage tracing indicated that early Osr1-positive cells can contribute not only to adipose tissue, but also to other mesoderm-derived tissues in defined embryonic regions.

From aorta to adipose

The anatomical clue to the origin and route of the progenitor cells emerged when the researchers examined embryos at the earlier stage using immunofluorescence: Osr1-positive cells were enriched in the dorsal aortic compartment, a narrow zone around the embryonic aorta. Over subsequent days, time-resolved tracing suggested that Osr1-lineage cells disperse from this area toward more back-and-side regions of the embryo (dorso-lateral territories).

This pattern is consistent with ideas about mesoangioblasts—vessel-associated, multipotent progenitors. The authors therefore propose that dorsal aorta–associated, Osr1-positive cells represent an in vivo source of progenitors that can later form several brown-fat depots.