Amazing stuff! We are still discovering new cell types!
"Researchers have discovered a new cell type that may help regulate blood vessel growth in the heart during development and in response to injury ... Working with zebrafish, they found that the new cell type helps stabilize the vascular network that supplies oxygen to growing cardiac muscle. ...
the epicardium, the thin layer of cells that surrounds the heart, provides both the signals and the cells needed to regenerate heart tissue in zebrafish. ...
One of these genes, a master regulator called scxa, directs progenitor cells to generate a previously uncharacterized cell type. These novel “perivascular” cells surround coronary blood vessels and express a type of collagen that regulates vascular development.
These perivascular cells also produce a signal – a small protein fragment derived from the collagen molecule – that ultimately reins in vessel expansion. ...
The findings suggest that low oxygen acts as an environmental cue, temporarily activating scxa, which directs a subset of epicardial progenitors toward a perivascular fate. They then surround coronary vessels and may help regulate their development and remodeling. ..."
From the abstract:
"The epicardium provides progenitor cells and paracrine signals essential for heart development and regeneration, yet the mechanisms regulating epicardial cell fate remain poorly understood.
Here, we identify the transcription factor Scleraxis a (scxa) as a key regulator of epicardial progenitor differentiation in zebrafish. Single-cell transcriptomics, genetic lineage tracing, and cardiac injury models reveal transient scxa expression in activated epicardial progenitor cells (aEPCs) during developmental coronary angiogenesis and heart regeneration.
scxa+ epicardial cells predominantly differentiate into a previously uncharacterized col18a1a+ perivascular population, termed epicardial-derived perivascular mesenchymal cells (Epi-PMCs), which is distinct from pericytes, vascular smooth muscle cells, and mammalian adventitial fibroblasts.
Epi-PMCs closely associate with coronary vessels and may contribute to vascular stabilization and remodeling, potentially through collagen XVIII.
Loss of scxa increases coronary vessel density. Hypoxia and Hif signaling induce scxa expression, identifying a hypoxia-responsive mechanism that promotes epicardial differentiation toward a vascular-supportive fate during heart development and regeneration."
Hypoxia-activated scleraxis a mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type (open access)
Fig. 1: scxa is expressed in differentiating epicardial progenitors during heart regeneration.
Fig. 2: Transient scxa+ epicardial cells are associated with coronary angiogenesis.
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