Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 793-803 ◽  
Author(s):  
M. Tavian ◽  
M.F. Hallais ◽  
B. Peault
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Sorting ◽  
Yolk Sac ◽  
Precursor Cell ◽  
Proliferative Potential ◽  
Semithin Section ◽  
Blood Stem Cells ◽  
Integrated Study

Hepatic hematopoiesis in the mouse embryo is preceded by two hematopoietic waves, one in the yolk sac, and the other in the paraaortic splanchnopleura, the presumptive aorta-gonad-mesonephros region that gives rise to prenatal and postnatal blood stem cells. An homologous intraembryonic site of stem cell emergence was previously identified at 5 weeks of human gestation, when hundreds of CD34(++)Lin- high-proliferative potential hematopoietic cells border the aortic endothelium in the preumbilical region. In the present study, we have combined immunohistochemistry, semithin section histology, fluorescence-activated cell sorting and blood cell culture in an integrated study of incipient hematopoiesis in the human yolk sac, truncal arteries and embryonic liver from 21 to 58 days of development. The chronology of blood precursor cell emergence in these distinct tissues suggests a pivotal role in the settlement of liver hematopoiesis of endothelium-associated stem cell clusters, which emerge not only in the dorsal aorta but also in the vitelline artery. Anatomic features and in vitro functionality indicate that stem cells develop intrinsically to embryonic artery walls from a presumptive territory whose blood-forming potential exists from at least 24 days of gestation.

scholarly journals An in vitro stem cell model of human epiblast and yolk sac interaction

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kirsty ML Mackinlay ◽  
Bailey AT Weatherbee ◽  
Viviane Souza Rosa ◽  
Charlotte E Handford ◽  
George Hudson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Human Embryo ◽  
Cell Model ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Embryonic Cells ◽  
Post Implantation

Human embryogenesis entails complex signalling interactions between embryonic and extra-embryonic cells. However, how extra-embryonic cells direct morphogenesis within the human embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in human embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the human embryo and propose YSLCs as a tool for studying post-implantation human embryo development in vitro.

scholarly journals ID3019 Female germline stem Cells: A source for application in reproductive and regenerative medicine

2017 ◽  
Vol 4 (S) ◽  
pp. 31
Author(s):  
Thuy Hong Bui
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Function ◽  
Primordial Germ Cells ◽  
Postnatal Life ◽  
Proliferative Potential ◽  
Germline Stem Cells ◽  
Mammalian Female ◽  
Female Germline

Studies suggest a renewable source of eggs and stir more controversy, especially about the origin of female germline stem cells (FGSCs). It should be elucidated whether or not neo-oogenesis continues in the ovaries of mammalian female during postnatal life. Therefore, the establishment of FGSCs is very important for many applications. Here, using adult pig ovary, we isolate, identify, characterize FGSCs to elucidate their origin, then examined the proliferation, growth and differentiation of them. These cells were heterogeneous, depending on both of c-kit expression and cell size, and also express stem cell and germ cell markers. Importantly, we show clearly that the cells with the characteristics of early primordial germ cells are present in the adult pig ovary. Once FGSCs were established, they could be expanded in vitro for months without loss of the identifying markers and proliferative potential. Under appropriate conditions, the FGSCs differentiated into primordial oocyte-like cells and grow close to full-sized oocytes. These may assist in therapeutic strategies in human with their potential to make new oocytes and support ovarian function and fertility. Our results support the theory that the ovary contains a small number of undifferentiated cells with stem cell characteristics. These might remain in the postnatal and adult ovary and under certain conditions could resume mitosis, enter meiosis and give rise to oocytes. Given the existence of these FGSCs in mammalian ovaries and the depletion in ovarian reserve during female reproductive aging, one can hypothesize that such “neo-oogenesis” was present in ancestral forms, is still present in insects, some fish and mollusks, but has been lost in land vertebrates through evolution. FGSCs cannot proliferate in the ovary normally because of inhibitory factors, but under appropriate conditions, they can undergo proliferation and differentiation, and provide a potential mechanism for the self-renewal of germline stem cells.

scholarly journals Distinct functional properties of highly purified hematopoietic stem cells from mouse strains differing in stem cell numbers

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1374-1379 ◽  
Author(s):  
Gerald de Haan ◽  
Stephen J. Szilvassy ◽  
Todd E. Meyerrose ◽  
Bert Dontje ◽  
Barry Grimes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Strains ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Transplant Patients ◽  
Hematopoietic Recovery ◽  
Functional Relevance

Abstract We have previously demonstrated that young adult DBA/2 (DBA) mice have more stem cells than C57BL/6 (B6) mice, as measured in a cobblestone area-forming cell (CAFC) assay using unfractionated marrow. To study the nature of this difference, we have now compared the proliferative fate of single, highly enriched Sca-1+c-kit+Lin−stem cells from these strains. Although equal in frequency, functional comparison revealed that Sca-1+c-kit+Lin−cells from DBA mice contained twice as many cells with CAFC activity. DBA clones persisted much longer in vitro, and developed later in time. To assess whether these differences were of any functional relevance in vivo, we compared engraftment of lethally irradiated mice transplanted with 1000 B6 or DBA Sca-1+c-kit+Lin−cells. Recipients of enriched DBA cells recovered much faster than animals transplanted with B6 cells. We also studied endogenous hematopoietic recovery after 5-fluorouracil (5-FU) treatment in vivo. Progenitors and peripheral blood cells recovered twice as fast in DBA mice. Thus, DBA stem cells have superior proliferative potential compared with phenotypically identical stem cells obtained from B6 mice. Such genetically determined quantitative and qualitative differences in stem cell behavior likely contribute to the dramatically different hematopoietic recovery rates observed in human transplant patients.

scholarly journals Distinct functional properties of highly purified hematopoietic stem cells from mouse strains differing in stem cell numbers

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1374-1379 ◽  
Author(s):  
Gerald de Haan ◽  
Stephen J. Szilvassy ◽  
Todd E. Meyerrose ◽  
Bert Dontje ◽  
Barry Grimes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Strains ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Transplant Patients ◽  
Hematopoietic Recovery ◽  
Functional Relevance

We have previously demonstrated that young adult DBA/2 (DBA) mice have more stem cells than C57BL/6 (B6) mice, as measured in a cobblestone area-forming cell (CAFC) assay using unfractionated marrow. To study the nature of this difference, we have now compared the proliferative fate of single, highly enriched Sca-1+c-kit+Lin−stem cells from these strains. Although equal in frequency, functional comparison revealed that Sca-1+c-kit+Lin−cells from DBA mice contained twice as many cells with CAFC activity. DBA clones persisted much longer in vitro, and developed later in time. To assess whether these differences were of any functional relevance in vivo, we compared engraftment of lethally irradiated mice transplanted with 1000 B6 or DBA Sca-1+c-kit+Lin−cells. Recipients of enriched DBA cells recovered much faster than animals transplanted with B6 cells. We also studied endogenous hematopoietic recovery after 5-fluorouracil (5-FU) treatment in vivo. Progenitors and peripheral blood cells recovered twice as fast in DBA mice. Thus, DBA stem cells have superior proliferative potential compared with phenotypically identical stem cells obtained from B6 mice. Such genetically determined quantitative and qualitative differences in stem cell behavior likely contribute to the dramatically different hematopoietic recovery rates observed in human transplant patients.

scholarly journals Ex vivo expansion of murine marrow cells with interleukin-3 (IL-3), IL- 6, IL-11, and stem cell factor leads to impaired engraftment in irradiated hosts

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 30-37 ◽  
Author(s):  
SO Peters ◽  
EL Kittler ◽  
HS Ramshaw ◽  
PJ Quesenberry
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Proliferative Potential ◽  
Interleukin 3 ◽  
Marrow Cells

Abstract In vitro incubation of bone marrow cells with cytokines has been used as an approach to expand stem cells and to facilitate retroviral integration. Expansion of hematopoietic progenitor cells has been monitored by different in vitro assays and in a few instances by in vivo marrow renewal in myeloablated hosts. This is the first report of studies, using two competitive transplant models, in which cytokine-treated cells, obtained from nonpretreated donors (eg, 5-fluorouracil), were competed with normal cells. A basic assumption is that the expansion of progenitors assayed in vitro as high- and low-proliferative potential colony-forming cells (HPP- and LPP-CFCs) indicates an expansion of stem cells which will repopulate in vivo. This study shows that culture of marrow cells with four cytokines (stem cell factor, interleukin-3 [IL-3], IL-6, IL-11) induces significant expansion and proliferation of HPP-CFC and LPP-CFC. Cell-cycle analysis showed that these hematopoietic progenitors were induced to actively cell cycle by culture with these cytokines. In the first competitive transplant model, which uses Ly5.2/Ly5.1 congenic mice, cytokine-cultured Ly5.2 cells competed with noncultured Ly5.1 cells led to 5% +/- 1% engraftment at 12 weeks and to 4% +/- 2% engraftment at 22 weeks posttransplantation for the cytokine exposed cells. Noncultured Ly5.2 cells competed with cultured Ly5.1 cells led to 70% +/- 1% engraftment at 12 weeks and to 93% +/- 2% engraftment at 22 weeks posttransplantation. In the second model, which uses BALB/c marrow of opposite genders, cultured male cells lead to 13% +/- 9% engraftment at 10 weeks and 2% +/- 1% engraftment at 14 weeks posttransplantation; noncultured male cells lead to 70% +/- 2% and 95% +/- 2% engraftment at 10 and 14 weeks posttransplantation, respectively. Data presented here from two different competitive transplant studies show a defect of cytokine expanded marrow related to cell cycle activation which manifests as defective long-term repopulating capability in irradiated host mice. The engraftment defect is more profound at longer time intervals, suggesting that the most striking effect may be on long-term repopulating cells.

scholarly journals Ex vivo expansion of murine marrow cells with interleukin-3 (IL-3), IL- 6, IL-11, and stem cell factor leads to impaired engraftment in irradiated hosts

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 30-37 ◽  
Author(s):  
SO Peters ◽  
EL Kittler ◽  
HS Ramshaw ◽  
PJ Quesenberry
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Proliferative Potential ◽  
Interleukin 3 ◽  
Marrow Cells

In vitro incubation of bone marrow cells with cytokines has been used as an approach to expand stem cells and to facilitate retroviral integration. Expansion of hematopoietic progenitor cells has been monitored by different in vitro assays and in a few instances by in vivo marrow renewal in myeloablated hosts. This is the first report of studies, using two competitive transplant models, in which cytokine-treated cells, obtained from nonpretreated donors (eg, 5-fluorouracil), were competed with normal cells. A basic assumption is that the expansion of progenitors assayed in vitro as high- and low-proliferative potential colony-forming cells (HPP- and LPP-CFCs) indicates an expansion of stem cells which will repopulate in vivo. This study shows that culture of marrow cells with four cytokines (stem cell factor, interleukin-3 [IL-3], IL-6, IL-11) induces significant expansion and proliferation of HPP-CFC and LPP-CFC. Cell-cycle analysis showed that these hematopoietic progenitors were induced to actively cell cycle by culture with these cytokines. In the first competitive transplant model, which uses Ly5.2/Ly5.1 congenic mice, cytokine-cultured Ly5.2 cells competed with noncultured Ly5.1 cells led to 5% +/- 1% engraftment at 12 weeks and to 4% +/- 2% engraftment at 22 weeks posttransplantation for the cytokine exposed cells. Noncultured Ly5.2 cells competed with cultured Ly5.1 cells led to 70% +/- 1% engraftment at 12 weeks and to 93% +/- 2% engraftment at 22 weeks posttransplantation. In the second model, which uses BALB/c marrow of opposite genders, cultured male cells lead to 13% +/- 9% engraftment at 10 weeks and 2% +/- 1% engraftment at 14 weeks posttransplantation; noncultured male cells lead to 70% +/- 2% and 95% +/- 2% engraftment at 10 and 14 weeks posttransplantation, respectively. Data presented here from two different competitive transplant studies show a defect of cytokine expanded marrow related to cell cycle activation which manifests as defective long-term repopulating capability in irradiated host mice. The engraftment defect is more profound at longer time intervals, suggesting that the most striking effect may be on long-term repopulating cells.

Stem Cells Derived from Human Exfoliated Deciduous teeth [shed] in Neuronal Disorders: A Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Minu Anoop ◽  
Indrani Datta
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Proliferative Potential ◽  
Pulp Tissue ◽  
Human Exfoliated Deciduous Teeth

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

scholarly journals Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

scholarly journals Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Manuel Pedro Jimenez-García ◽  
Antonio Lucena-Cacace ◽  
Daniel Otero-Albiol ◽  
Amancio Carnero
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Neural Crest ◽  
Tumor Suppressors ◽  
Homeobox Genes ◽  
Neuronal Cell ◽  
Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

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