PT  - JOURNAL ARTICLE
AU  - Ana E. Jenike
AU  - Katharine M. Jenike
AU  - Kevin J. Peterson
AU  - Bastian Fromm
AU  - Marc K. Halushka
TI  - Direct observation of the evolution of cell-type specific microRNA expression signatures supports the hematopoietic origin model of endothelial cells
AID  - 10.1101/2022.11.23.517662
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.23.517662
4099  - http://biorxiv.org/content/early/2022/11/24/2022.11.23.517662.short
4100  - http://biorxiv.org/content/early/2022/11/24/2022.11.23.517662.full
AB  - The evolution of specialized cell-types is a long-standing interest of biologists, but given the deep time-scales very difficult to reconstruct or observe. microRNAs have been linked to the evolution of cellular complexity and may inform on specialization. The endothelium is a vertebrate specific specialization of the circulatory system that enabled a critical new level of vasoregulation. The evolutionary origin of these endothelial cells is unclear. We hypothesized that Mir-126, an endothelial cell-specific microRNA may be informative.We here reconstruct the evolutionary history of Mir-126. Mir-126 likely appeared in the last common ancestor of vertebrates and tunicates, a species without an endothelium, within an intron of the evolutionary much older EGF Like Domain Multiple (Egfl) locus. Mir-126 has a complex evolutionary history due to duplications and losses of both the host gene and the microRNA. Taking advantage of the strong evolutionary conservation of the microRNA among Olfactores, and using RNA in situ hybridization (RISH), we localized Mir-126 in the tunicate Ciona robusta. We found exclusive expression of the mature Mir-126 in granular amebocytes, supporting a long-proposed scenario that endothelial cells arose from hemoblasts, a type of proto-endothelial amoebocyte found throughout invertebrates.This observed change of expression of Mir-126 from proto-endothelial amoebocytes in the tunicate to endothelial cells in vertebrates is the first direct observation of the evolution of a cell-type in relation to microRNA expression indicating that microRNAs can be a prerequisite of cell-type evolution.Research Highlightsdirect observation of cell-type evolutionhigh conservation of sequence enables for simple RISH experiment of expressionMir-126 follows the evolution of hematopoetic cells to endothelial cellsCompeting Interest StatementThe authors have declared no competing interest.