Capturing Pluripotency and Beyond

During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast’s identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.

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G2M splits mouse embryonic stem cells into naïve and formative pluripotency states

10.1101/616516 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kersti Jääger ◽

Daniel Simpson ◽

Maria Kalantzaki ◽

Angela Salzano ◽

Ian Chambers ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Transcriptional Control ◽

Embryonic Stem ◽

Human Escs ◽

Lineage Specification ◽

New Framework

ABSTRACTEmbryonic stem cells (ESCs) express heterogeneous levels of pluripotency and developmental transcription factors (TFs) and their cell cycle is unsynchronised when grown in the presence of serum. Here, we asked whether the cell cycle and developmental heterogeneities of ESCs are coordinated by determining the state identities of G1- and G2M-enriched mouse ESCs (mESCs) at single cell resolution. We found that G2M cells were not all the same and demonstrate their split into the naïve and formative (intermediate) pluripotency states marked by high or low Esrrb expression, respectively. The naïve G2M sub-state resembles ‘ground’ state pluripotency of the LIF/2i cultured mESCs. The naïve and formative G2M sub-states exist in the pre- and post-implantation stages of the mouse embryo, respectively, verifying developmental distinction. Moreover, the G2M sub-states partially match between the mouse and human ESCs, suggesting higher similarity of transcriptional control between these species in G2M. Our findings propose a model whereby G2M separates mESCs into naïve and formative pluripotency states. This concept of G2M-diverted pluripotency states provides new framework for understanding the mechanisms of pluripotency maintenance and lineage specification in vitro and in vivo, and the development of more efficient and clinically relevant reprogramming strategies.

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Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200116100121 ◽

2020 ◽

Vol 15 (4) ◽

pp. 301-307 ◽

Cited By ~ 3

Author(s):

Gaifang Wang ◽

Maryam Farzaneh

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Human Pluripotent Stem Cells ◽

Human Oocyte ◽

Differentiation Potential ◽

Cell Lineages ◽

Cell Based Therapy ◽

Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

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Mouse Androgenetic Embryonic Stem Cells Differentiated to Multiple Cell Lineages in Three Embryonic Germ Layers In Vitro

Journal of Reproduction and Development ◽

10.1262/jrd.20146 ◽

2009 ◽

Vol 55 (3) ◽

pp. 283-292 ◽

Cited By ~ 8

Author(s):

Takeshi TERAMURA ◽

Yuta ONODERA ◽

Hideki MURAKAMI ◽

Syunsuke ITO ◽

Toshihiro MIHARA ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Germ Layers ◽

Cell Lineages ◽

Multiple Cell

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Function of Pumilio Genes in Human Embryonic Stem Cells and Their Effect in Stemness and Cardiomyogenesis

10.1101/751537 ◽

2019 ◽

Author(s):

Isabelle Leticia Zaboroski Silva ◽

Anny Waloski Robert ◽

Guillermo Cabrera Cabo ◽

Lucia Spangenberg ◽

Marco Augusto Stimamiglio ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Rna Binding ◽

Rna Binding Proteins ◽

Embryonic Stem ◽

Mrna Levels ◽

Human Escs ◽

Mrna Targets ◽

Cardiomyogenic Differentiation

AbstractPosttranscriptional regulation plays a fundamental role in the biology of embryonic stem cells (ESCs). Many studies have demonstrated that multiple mRNAs are coregulated by one or more RNA binding proteins (RBPs) that orchestrate the expression of these molecules. A family of RBPs, known as PUF (Pumilio-FBF), is highly conserved among species and has been associated with the undifferentiated and differentiated states of different cell lines. In humans, two homologs of the PUF family have been found: Pumilio 1 (PUM1) and Pumilio 2 (PUM2). To understand the role of these proteins in human ESCs (hESCs), we first demonstrated the influence of the silencing of PUM1 and PUM2 on pluripotency genes. OCT4 and NANOG mRNA levels decreased significantly with the knockdown of Pumilio, suggesting that PUMILIO proteins play a role in the maintenance of pluripotency in hESCs. Furthermore, we observed that the hESCs silenced for PUM1 and 2 exhibited an improvement in efficiency of in vitro cardiomyogenic differentiation. Using in silico analysis, we identified mRNA targets of PUM1 and PUM2 expressed during cardiomyogenesis. With the reduction of PUM1 and 2, these target mRNAs would be active and could be involved in the progression of cardiomyogenesis.

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B-1 lymphoid cells develop independently of Notch signaling during mouse embryonic development

10.1101/2020.11.09.375634 ◽

2020 ◽

Author(s):

Nathalia Azevedo ◽

Elisa Bertesago ◽

Ismail Ismailoglu ◽

Michael Kyba ◽

Michihiro Kobayashi ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Development ◽

Blood Cell ◽

Notch Signaling ◽

Embryonic Stem ◽

Cell Types ◽

Lymphoid Cells ◽

Lineage Specification ◽

Hematopoietic Stem

AbstractThe in vitro generation from pluripotent stem cells (PSCs) of different blood cell types, in particular those that are not replenished by hematopoietic stem cells (HSCs) like fetal-derived tissue-resident macrophages and innate-like lymphocytes, is of a particular interest. In order to succeed in this endeavor, a thorough understanding of the pathway interplay promoting lineage specification for the different blood cell types is needed. Notch signaling is essential for the HSC generation and their derivatives, but its requirement for tissue-resident immune cells is unknown. Using mouse embryonic stem cells (mESCs) to recapitulate murine embryonic development, we have studied the requirement for Notch signaling during the earliest B-lymphopoiesis and found that Rbpj-deficient mESCs are able to generate B-1 cells. Their Notch-independence was confirmed in ex vivo experiments using Rbpj-deficient embryos. In addition, we found that upregulation of Notch signaling was needed for the emergence of B-2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dosage is critical for the different B-cell lineage specification and provides pivotal information for their in vitro generation from PSCs for therapeutic applications.

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Temporal and epigenetic regulation of neurodevelopmental plasticity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2006.2010 ◽

2007 ◽

Vol 363 (1489) ◽

pp. 23-38 ◽

Cited By ~ 21

Author(s):

Nicholas D Allen

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Developmental Plasticity ◽

Neural Progenitor Cells ◽

Embryonic Stem ◽

Neural Progenitor ◽

Neural Progenitors ◽

Developmental Potential ◽

Neural Lineage

The anticipated therapeutic uses of neural stem cells depend on their ability to retain a certain level of developmental plasticity. In particular, cells must respond to developmental manipulations designed to specify precise neural fates. Studies in vivo and in vitro have shown that the developmental potential of neural progenitor cells changes and becomes progressively restricted with time. For in vitro cultured neural progenitors, it is those derived from embryonic stem cells that exhibit the greatest developmental potential. It is clear that both extrinsic and intrinsic mechanisms determine the developmental potential of neural progenitors and that epigenetic, or chromatin structural, changes regulate and coordinate hierarchical changes in fate-determining gene expression. Here, we review the temporal changes in developmental plasticity of neural progenitor cells and discuss the epigenetic mechanisms that underpin these changes. We propose that understanding the processes of epigenetic programming within the neural lineage is likely to lead to the development of more rationale strategies for cell reprogramming that may be used to expand the developmental potential of otherwise restricted progenitor populations.

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Full-term development of enucleated mouse oocytes fused with embryonic stem cells from different cell lines

Reproduction ◽

10.1530/rep.0.1210729 ◽

2001 ◽

pp. 729-733 ◽

Cited By ~ 25

Author(s):

T Amano ◽

Y Kato ◽

Y Tsunoda

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Cell Lines ◽

Formation Rate ◽

Embryonic Stem ◽

Clear Correlation ◽

Developmental Potential ◽

Mouse Oocytes

The developmental potential of enucleated mouse oocytes receiving embryonic stem cells from ten lines with either the same or different genetic backgrounds using the cell fusion method was examined in vitro and in vivo. The development of nuclear-transferred oocytes into blastocysts was high (34-88%). However, there was no clear correlation between development into blastocysts after nuclear transfer and the chimaera formation rate of embryonic stem cells. The development into live young was low (1-3%) in all cell lines and 14 of 19 young died shortly after birth. Most of the live young had morphological abnormalities. Of the five remaining mice, two died at days 23 and 30 after birth, but the other three mice are still active at days 359 (mouse 1) and 338 (mice 4 and 5) after birth, with normal fertility. However, the reasons for the abnormalities and postnatal death of embryonic stem cell-derived mice are unknown.

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