Why are hematopoietic stem cells so ‘sexy’? on a search for developmental explanation

Abstract

Evidence has accumulated that normal human and murine hematopoietic stem cells express several functional pituitary and gonadal sex hormones and that, in fact, some sex hormones, such as androgens, have been employed for many years to stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex hormone receptors are also expressed by leukemic cell lines and blasts. In this review I will discuss the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that precursors of hematopoietic stem cells are related to subpopulation of migrating primordial germ cells. To support of this notion, the anatomical sites of origin of primitive and definitive hematopoiesis during embryonic development are tightly connected with the migratory route of primordial germ cells: from the proximal epiblast to the extraembryonic endoderm at the bottom of the yolk sac and then back to the embryo proper via the primitive streak to the aorta-gonado-mesonephros (AGM) region on the way to the genital ridges. The migration of these cells overlaps with the emergence of primitive hematopoiesis in the blood islands at the bottom of the yolk sac, and definitive hematopoiesis that occurs in hemogenic endothelium in the embryonic dorsal aorta in AGM region.

Elevated Numbers of Circulating Very Small Embryonic-Like Stem Cells (VSELs) and Intermediate CD14++CD16+ Monocytes in IgA Nephropathy

“…However, to date, it remains elusive whether pathological changes observed in IgAN are somehow counteracted by the activation of any regenerative mechanisms related to stem cells or other cells with regenerative potential. Stem cells with highest regenerative potential such as hematopoietic stem cells (HSCs), very small embryonic like cells (VSELs), epithelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) can be found in bone marrow [ 2 , 3 ]. Importantly, several reports indicated that bone marrow derived stem cells may support regeneration of such distant tissues as kidney [ 4 ].…”

The DLK1-MEG3 locus in malignant cells of proposed primordial germ cell origins.

“…Interestingly, there are significant overlaps between the transitions into and out of proliferation by PGCs and changes to their epigenome ( Figure 5A) [41]. Similarly, this timeframe also overlaps with the first signs of hematopoiesis in the embryo [42]. Importantly, though these cells are derivatives of ESCs, which are capable of forming teratomas in vivo, PGCs are not able to form teratomas.…”

“…The appearance of PGCs at the allantois, a region of the extraembryonic yolk sac, at E7.5 occurs at a similar time and region as the first appearance of hemangioblasts and hematopoietic islands [90,91]. Similarly, PGCs enter the aorta-gonad-mesonsephros region of the embryo at E11, which is the region where HSCs first appear and where Oct3/4-expressing cells were recently isolated which could form hematopoietic colonies in vitro [42,92].…”

“…Several lines of evidence place HSCs and VSELs as derivatives of migrating PGCs in the developing embryo [42]. Similarly, TGCTs are proposed to originate from PGCs at various stages of their development [36].…”

“…PGCs serve as the proposed origin of HSCs, VSELs, and TGCTs such as EC [42][43][44]. Thus, it is interesting that TGCTs display such malignant growth while exhibiting hypomethylation at the IGF2/H19 ICR [36][37][38].…”