DLK-1 as a Marker to Distinguish Unrestricted Somatic Stem Cells and Mesenchymal Stromal Cells in Cord Blood

Abstract

In addition to hematopoietic stem cells, cord blood (CB) also contains different nonhematopoietic CD45-, CD34- adherent cell populations: cord blood mesenchymal stromal cells (CB MSC) that behave almost like MSC from bone marrow (BM MSC) and unrestricted somatic stem cells (USSC) that differentiate into cells of all 3 germ layers. Distinguishing between these populations is difficult due to overlapping features such as the immunophenotype or the osteogenic and chondrogenic differentiation pathway. Functional differences in the differentiation potential suggest different developmental stages or different cell populations. Here we demonstrate that the expression of genes and the differentiation toward the adipogenic lineage can discriminate between these 2 populations. USSC, including clonal-derived cells lacking adipogenic differentiation, strongly expressed δ-like 1/preadipocyte factor 1 (DLK-1/PREF1) correlating with high proliferative potential, while CB MSC were characterized by a strong differentiation toward adipocytes correlating with a weak or negative DLK-1/PREF1 expression. Constitutive overexpression of DLK-1/PREF1 in CB MSC resulted in a reduced adipogenic differentiation, whereas silencing of DLK-1 in USSC resulted in adipogenic differentiation.

Small Molecule Mesengenic Induction of Human Induced Pluripotent Stem Cells to Generate Mesenchymal Stem/Stromal Cells

“…Although all cell types differentiated, their data instead show that the degree to which each cell line differentiated was different and support our findings and those in the literature that fetal, ES-, and iPS-MSCs have less adipogenicity than adult bone marrow MSCs. The reasons for this are not known, although ontological differences in inhibitory DLK-1/ PREF1 expression is one possibility [37,58]. It is also well known in the field that MSC trilineage differentiation of is also dependent on intrinsic factors, including age of donor [3,4], genotype of donor [59], and tissue of origin [34,39,60], as well as in vitro parameters, including culture medium, substrate, and two-versus three-dimensional culture [61][62][63].…”

Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

“…+++ [7] HOX-gene [7] , DLK-1 [16] , pSmad2 (low and modulated) [12] Negative for: CD14, CD34 [1] , CD56 [7] UC-MSC Positive for: CD90, CD73, CD105, CD13, CD44 [1] PAI-1, MnSOD [10] , HOX-gene (different expression pattern) [7] Reports for adipo- [13,15] and osteogenic [7,12] differentiation failure CD56, CD146…”

“…Comparative of MSC from cord-matrix and bone-marrow was inversely correlated with DLK-1 expression in mesenchymal stem cells isolated from cord blood-MSC (CB-MSC). UC-MSCs do not or weakly express DLK-1; which can explain their failure to differentiate into adipocytes [16] . Bosch et al [7] , went further by wondering if UC-MSC are true "mesenchymal stromal stem cells".…”

Unrestricted somatic stem cells differentiation into hepatic-like cells in a three dimensional arrangement

“…CB-MSC and unrestricted somatic stem cells (USSC) share many overlapping features concerning the immunophenotype and differentiation potential. Compared to CB-MSC, USSC have a limited adipogenic differentiation potential associated with a strong expression of delta-like 1/ pre-adipocyte factor 1 (DLK-1/PREF1) (12). DLK1 is referred to as a fetal and immature tissue marker, expressed in multiple embryonic tissues but downregulated in the majority of postnatal cells.…”