The transcription factor complex LMO2/TAL1 regulates branching and endothelial cell migration in sprouting angiogenesis

Abstract

The transcription factor complex, consisting of LMO2, TAL1 or LYL1, and GATA2, plays an important role in capillary sprouting by regulating VEGFR2, DLL4, and angiopoietin 2 in tip cells. Overexpression of the basic helix-loop-helix transcription factor LYL1 in transgenic mice results in shortened tails. This phenotype is associated with vessel hyperbranching and a relative paucity of straight vessels due to DLL4 downregulation in tip cells by forming aberrant complex consisting of LMO2 and LYL1. Knockdown of LMO2 or TAL1 inhibits capillary sprouting in spheroid-based angiogenesis assays, which is associated with decreased angiopoietin 2 secretion. In the same assay using mixed TAL1- and LYL1-expressing endothelial cells, TAL1 was found to be primarily located in tip cells, while LYL1-expressing cells tended to occupy the stalk position in sprouts by upregulating VEGFR1 than TAL1. Thus, the interaction between LMO2 and TAL1 in tip cells plays a key role in angiogenic switch of sprouting angiogenesis.

Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells

“…S7G). Consistently, gene expression analysis indicated markedly down-regulated expression of fosl1a and raldh2, as well as tal1, which also labels aECs around the wound area at 7 dpa (31)(32)(33)(34), in EC:dnAP-1 hearts compared to controls (fig. S7H).…”

Identification of a minority population of LMO2 + breast cancer cells that integrate into the vasculature and initiate metastasis

“…We next measured the relative abundance of distinct endothelial, immune, stromal, and epithelial populations in human breast tumors with respect to LMO2 + basal cells. As LMO2 is expressed in multiple cell types, including immune, stromal, and endothelial cells (ECs) ( 21 , 24 , 25 ), the expression of this gene is insufficient to distinguish cell types. Therefore, we defined unique transcriptional signatures for various niche and breast epithelial cells from our scRNA-seq data and used CIBERSORTx to calculate the cellular composition of bulk RNA admixtures from breast cancer clinical cohorts ( 26 ) (Materials and Methods).…”

“…LMO2 has been extensively studied in hematological malignancies ( 22 , 39 ) and ECs ( 24 , 33 ) and is well established as a transcriptional adaptor protein ( 25 ). Recent studies have attempted to understand the role of LMO2 in breast cancer ( 34 , 55 ) but have suffered from contradictory results, were limited to cell lines, and did not attribute LMO2 to any particular tumor cell population.…”