STELLA collaborates in distinct mesendodermal cell subpopulations at the fetal-placental interface in the mouse gastrula

Abstract

The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface. Thus, if PGCs form extragonadally within the posterior region of the mammal, they cannot be distinguished from the soma on the basis of these proteins. We used immunohistochemistry, immunofluorescence, and confocal microscopy of the mouse gastrula to co-localize STELLA with a variety of gene products, including pluripotency factor OCT-3/4, mesendoderm-associated T and MIXl1, mesendoderm- and endoderm-associated FOXa2 and hematopoietic factor Runx1. While a subpopulation of cells localizing OCT-3/4 was always found independently of STELLA, STELLA always co-localized with OCT-3/4. Despite previous reports that T is involved in specification of the germ line, co-localization of STELLA and T was detected only in a small subset of cells in the base of the allantois. Slightly later in the hindgut lip, STELLA+/(OCT-3/4+) co-localized with FOXa2, as well as with RUNX1, indicative of definitive endoderm and hemangioblasts, respectively. STELLA was never found with MIXl1. On the basis of these and previous results, we conclude that STELLA identifies at least five distinct cell subpopulations within the allantois and hindgut, where they may be involved in mesendodermal differentiation and hematopoiesis at the posterior embryonic-extraembryonic interface. These data provide a new point of departure for understanding STELLA’s potential roles in building the fetal-placental connection.

Bioengineered embryoids mimic post-implantation development in vitro

“…We did not detect Sox17-positive cells in embryoids that initiated T/Bra expression, but we could detect some Dppa3-positive cells ( Supplementary Fig. 5b), likely marking primordial germ cell (PGC) progenitors 28 .…”

The mouse fetal‐placental arterial connection: A paradigm involving the primitive streak and visceral endoderm with implications for human development

“…With a reliable whole embryo culture system, carefully staged embryos (Downs & Davies, ) can be analyzed at intervals of 2–4 hr, which is the length of time it takes to pass from one stage to the next (Downs & Gardner, ); up to 18 stages are often studied for any given question (Daane et al, ; Daane & Downs, ; Downs, ; Downs, Inman, Jin, & Enders, ; Inman & Downs, , ; Mikedis & Downs, , ; Rodriguez et al, ; Rodriguez & Downs, ; Wolfe & Downs, ; Wolfe, Rodriguez, & Downs, ). To ascertain involvement of specific cell types, analysis is typically carried out in at least two orientations, sagittal and transverse, in histological and/or immunohistochemical preparations.…”

“…The AX and the hindgut lip exhibit similar mesendodermal proteins (Downs et al, ; Kanai‐Azuma et al, ; Wolfe et al, ; Wolfe & Downs, ). Moreover, levels of Ptch1 are low in the hindgut lip but high in the dAX, with which the hindgut lip is also continuous (Rodriguez & Downs, ) (Figure a,b).…”

“…Visceral endoderm's requirement in antero‐posterior function of the primitive streak is reminiscent of previous results which showed that hepatic nuclear factor‐3‐beta (HNF3B, or FOXa2) in visceral endoderm is critical for morphogenesis of the primitive streak and thus, antero‐posterior polarity (Dufort et al, ). Intriguingly, FOXa2 protein is found uniquely within the AX (Wolfe et al, ) prior to its transformation into the rod (Rodriguez & Downs, ).…”

Dppa3 in pluripotency maintenance of ES cells and early embryogenesis

“…39 Dppa3 appears at least in five distinct cell subgroups within the hindgut and allantois, where they may be related to mesodermal differentiation and hematopoiesis at the posterior fetal-placental connection. 38 Dppa3 participates in different mesodermal cell subgroups of the fetal-placental interface in the mouse embryos.…”