Human and Murine Very Small Embryonic-Like Cells Represent Multipotent Tissue Progenitors, In Vitro and In Vivo

Havens, Aaron M.; Sun, Hongli; Shiozawa, Yusuke; Jung, Younghun; Wang, Jingcheng; Mishra, Anjali; Jiang, Yang; O’Neill, David; Krebsbach, Paul H.; Rodgerson, Denis O.; Taichman, Russell S.

doi:10.1089/scd.2013.0362

Cited by 73 publications

(63 citation statements)

References 41 publications

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“…Moreover, recent reports on the existence of developmentally early stem cells with broader specification potential in BM [5,11] pose two of the most important questions in developmental biology: What is the hierarchy within the stem cell compartment in murine BM, and are there remnants of embryonic development found in adult BM [5,[29][30][31][32][33][34][35][36]?…”

Section: Discussionmentioning

confidence: 99%

“…These cells sorted based on surface markers and small size seem to be still somehow heterogeneous as revealed by gene expression analysis performed on single sorted murine VSELs [42]. However, what is important, they show multilineage differentiation potential into all three germ layers [34][35][36]40] and, under appropriate coculture conditions with OP-9 stromal cells, some of them can be specified into HSPCs [17,18]. They express embryonic stem cell markers such as Oct-4 and Nanog in their nuclei, and some murine VSELs express several markers, including Stella, Prdm14, Fragilis, Blimp1, Nanos3, and Dnd1, which are shared with migratory PGCs [11].…”

Section: Cd45mentioning

confidence: 99%

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Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

Mierzejewska

Borkowska

Suszyńska

et al. 2015

Stem Cells and Development

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Evidence has accumulated that hematopoietic stem progenitor cells (HSPCs) share several markers with the germline, a connection supported by reports that prolactin, androgens, and estrogens stimulate hematopoiesis. To address this issue more directly, we tested the expression of receptors for pituitary-derived hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), on purified murine bone marrow (BM) cells enriched for HSPCs and tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. We also tested whether administration of pituitary-and gonad-derived sex hormones (SexHs) increases incorporation of bromodeoxyuridine (BrdU) into HSPCs and expansion of hematopoietic clonogenic progenitors in mice and promotes recovery of blood counts in sublethally irradiated animals. We report for the first time that HSPCs express functional FSH and LH receptors and that both proliferate in vivo and in vitro in response to stimulation by pituitary SexHs. Furthermore, based on our observations that at least some of CD45 -very small embryonic-like stem cells (VSELs) may become specified into CD45+ HSPCs, we also evaluated the expression of pituitary and gonadal SexHs receptors on these cells and tested whether these quiescent cells may expand in vivo in response to SexHs administration. We found that VSELs express SexHs receptors and respond in vivo to SexHs stimulation, as evidenced by BrdU accumulation. Since at least some VSELs share several markers characteristic of migrating primordial germ cells and can be specified into HSPCs, this observation sheds new light on the BM stem cell hierarchy.

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Section: Discussionmentioning

confidence: 99%

Section: Cd45mentioning

confidence: 99%

Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

Mierzejewska

Borkowska

Suszyńska

et al. 2015

Stem Cells and Development

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“…VSELs have a huge motility and are theoretically able to migrate from bone marrow to vessels. They have all the characteristics of potential vasculogenic CD45negative stem cells able to give rise to vessels since they have been described to differentiate in endothelial cells by several independent groups with human, mouse or rat VSELs [6,30,31].…”

Section: Editorialmentioning

confidence: 99%

Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

Smadja

2017

Stem Cell Rev and Rep

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Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here. This paper allows one to better appreciate bone marrow-VSELs differentiation potential and opens new perspectives for autologous cell therapy. Furthermore, it might help explaining lots of contradictive data from the past 20 years, in particular related to ability of bone marrow cells to differentiate into cardiomyocytes.

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“…They survive in all adult body organs (not restricted only to the gonads) and serve as a backup pool for various tissue specific stem/ progenitor cells throughout life (35,36). Also besides expressing pluripotent and PGC-specific markers, VSELs obtained from both mouse bone marrow [(37) and personal observations] and human cord blood (38) have the ability to differentiate into 3 germ layers in vitro. Scientific community needs to be convinced about the existence of VSELs and their potential.…”

Section: Commentarymentioning

confidence: 99%

Making gametes from pluripotent stem cells: embryonic stem cells or very small embryonic-like stem cells?

Bhartiya¹,

Anand²,

Patel³

2016

Stem Cell Investig.

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Human and Murine Very Small Embryonic-Like Cells Represent Multipotent Tissue Progenitors, In Vitro and In Vivo

Cited by 73 publications

References 41 publications

Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

Making gametes from pluripotent stem cells: embryonic stem cells or very small embryonic-like stem cells?

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