Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification

Mapping Intimacies ◽

10.1101/2021.11.02.465785 ◽

2021 ◽

Author(s):

Francesca M Aloisio ◽

Diane L Barber

Keyword(s):

Stem Cells ◽

Embryonic Development ◽

Nuclear Translocation ◽

Morphological Changes ◽

Embryonic Stem ◽

Complex Activity ◽

Lineage Specification ◽

Epithelial Plasticity ◽

Established Role

Mouse embryonic stem cells (mESCs), a model for differentiation into primed epiblast-like cells (EpiLCs), have revealed transcriptional and epigenetic control of early embryonic development. The control and significance of morphological changes, however, remain less defined. We show marked changes in morphology and actin architectures during differentiation that depend on Arp2/3 complex but not formin activity. Inhibiting Arp2/3 complex activity pharmacologically or genetically does not block exit from naive pluripotency but attenuates increases in EpiLC markers. We find that inhibiting Arp2/3 complex activity delays formative pluripotency and causes globally defective lineage specification as indicated by RNA-sequencing, with significant effects on TBX3-depedendent transcriptional programs. We also identify two previously unreported indicators of mESC differentiation; MRTF and FHL2, which have inverse Arp2/3 complex-dependent nuclear translocation. Our findings on Arp2/3 complex activity in differentiation and the established role of formins in EMT indicate that these two actin nucleators regulate distinct modes of epithelial plasticity.

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

Development ◽

10.1242/dev.199373 ◽

2021 ◽

Author(s):

Nathalia Azevedo Portilho ◽

Rebecca Scarfò ◽

Elisa Bertesago ◽

Ismail Ismailoglu ◽

Michael Kyba ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Development ◽

Notch Signaling ◽

Ex Vivo ◽

Embryonic Stem ◽

Lymphoid Cells ◽

Fetal Life ◽

Lineage Specification ◽

Hematopoietic Stem

B-1 lymphocytes are a small but unique component of the innate immune-like cells. However, their ontogenic origin is still a matter of debate. While it is widely accepted that B-1 cells originate early in fetal life, whether or not they arise from hematopoietic stem cells (HSCs) is still unclear. In order to shed light on the B-1 cell origin, we set out to determine whether their lineage specification is dependent on Notch signaling, which is essential for the HSC generation and therefore, all derivatives lineages. 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 induced the emergence of B-2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dosage is critical for different B-cell lineages specification from endothelial cells and provides pivotal information for their in vitro generation from PSCs for therapeutic applications.

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The roles of ERAS during cell lineage specification of mouse early embryonic development

Open Biology ◽

10.1098/rsob.150092 ◽

2015 ◽

Vol 5 (8) ◽

pp. 150092 ◽

Cited By ~ 13

Author(s):

Zhen-Ao Zhao ◽

Yang Yu ◽

Huai-Xiao Ma ◽

Xiao-Xiao Wang ◽

Xukun Lu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Embryonic Stem Cells ◽

Embryonic Development ◽

Expression Pattern ◽

Embryonic Stem ◽

Cell Lineage ◽

Primitive Streak ◽

Early Embryonic Development ◽

Lineage Specification

Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the β -catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development.

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Faculty Opinions recommendation of Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8379957.8827055 ◽

2011 ◽

Author(s):

Iannis Aifantis

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Cell Lineage ◽

Mouse Embryonic Stem Cells ◽

Lineage Specification

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The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

Nucleic Acids Research ◽

10.1093/nar/27.16.3276 ◽

1999 ◽

Vol 27 (16) ◽

pp. 3276-3282 ◽

Cited By ~ 65

Author(s):

P. P. H. Van Sloun ◽

J. G. Jansen ◽

G. Weeda ◽

L. H. F. Mullenders ◽

A. A. van Zeeland ◽

...

Keyword(s):

Stem Cells ◽

Dna Damage ◽

Embryonic Stem Cells ◽

Nucleotide Excision Repair ◽

Excision Repair ◽

Embryonic Stem ◽

Genotoxic Effects ◽

Nucleotide Excision

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Modulation of Differentiation of Embryonic Stem Cells by Polypyrrole: The Impact on Neurogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22020501 ◽

2021 ◽

Vol 22 (2) ◽

pp. 501

Author(s):

Kateřina Skopalová ◽

Katarzyna Anna Radaszkiewicz ◽

Věra Kašpárková ◽

Jaroslav Stejskal ◽

Patrycja Bober ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Active Role ◽

Low Molecular Weight ◽

Conducting Materials ◽

The Impact ◽

Erk Kinase

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

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