Evidence for novel fate of Flk1⁺ progenitor: Contribution to muscle lineage

Abstract

Flk1 is one of the specific cell surface receptors for vascular endothelial growth factor and one of the most specific markers highlighting the earliest stage of hematopoietic and vascular lineages. However, recent new evidence suggests that these Flk1(+) mesodermal progenitor cells also contribute to muscle lineages. All evidence is based on the experiments using in vitro differentiation and in vivo transplantation systems. Although this approach revealed a differentiation potential range of Flk1(+) cells that is wider than previously expected, it fails to determine whether Flk1(+) cells contribute to muscle lineage as part of the normal developmental process. To obtain direct evidence for the fate of Flk1(+) cells in development, we used a knock-in mouse line where Cre is expressed in Flk1(+) cells. Studies with these Cre lines provide direct evidence that Flk1(+) cells are progenitors for muscles, in addition to hematopoietic and vascular endothelial cells.

Wnt2 Coordinates the Commitment of Mesoderm to Hematopoietic, Endothelial, and Cardiac Lineages in Embryoid Bodies

“…Blast colony-forming cells (BLCFCs) derived from EBs can generate hematopoietic and endothelial cell lineages, and represent the long-hypothesized hemangioblast (13,14). Flk1 ϩ cells may also give rise to smooth muscle cells (SMC) and cardiomyocytes under appropriate culture conditions (15)(16)(17).…”

“…Blast colony-forming cells (BLCFCs) derived from EBs can generate hematopoietic and endothelial cell lineages, and represent the long-hypothesized hemangioblast (13,14). Flk1 ϩ cells may also give rise to smooth muscle cells (SMC) and cardiomyocytes under appropriate culture conditions (15)(16)(17).Wnts are paracrine/autocrine signaling molecules that have been implicated in many aspects of normal development. Canonical Wnt signaling acts through ␤-catenin and T-cell factor/lymphoid enhancer factor transcriptional factors that regulate target gene expression (reviewed in Refs.…”

VE‐cadherin‐CreERT2 transgenic mouse: A model for inducible recombination in the endothelium

“…In the case of endothelial-specific gene targeting, several Cre lines have been developed with varying degrees of endothelial specificity (Gustafsson et al, 2001;Kisanuki et al, 2001;Motoike et al, 2003;Alva et al, 2006). Although extremely informative, the deletion of a wide array of genes using these lines has resulted in hemorrhage and eventual embryonic lethality.…”

Myeloid Cells and Lymphangiogenesis

“…In mice, definitive hematopoietic stem cells are derived from a socalled hemogenic endothelium. Lineage tracing studies have shown that most leukocytes originate from cells expressing endothelial markers (found on blood vessel endothelial cells [BECs] during development and in the adult), including vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial cadherin (VE-Cadherin) or Tie-2/TEK (Motoike et al 2003;Chen et al 2009). Hence, a hematopoietic system cannot be established in the absence of a primitive endothelial system.…”