Human Embryonic Stem Cell Responses to Ionizing Radiation Exposures: Current State of Knowledge and Future Challenges

Human embryonic stem cells, which are derived from the inner cell mass of the blastocyst, have become an object of intense study over the last decade. They possess two unique properties that distinguish them from many other cell types: (i) the ability to self-renew indefinitely in culture under permissive conditions, and (ii) the pluripotency, defined as the capability of giving rise to all cell types of embryonic lineage under the guidance of the appropriate developmental cues. The focus of many recent efforts has been on the elucidating the signaling pathways and molecular networks operating in human embryonic stem cells. These cells hold great promise in cell-based regenerative therapies, disease modeling, drug screening and testing, assessing genotoxic and mutagenic risks associated with exposures to a variety of environmental factors, and so forth. Ionizing radiation is ubiquitous in nature, and it is widely used in diagnostic and therapeutic procedures in medicine. In this paper, our goal is to summarize the recent progress in understanding how human embryonic stem cells respond to ionizing radiation exposures, using novel methodologies based on “omics” approaches, and to provide a critical discussion of what remains unknown; thus proposing a roadmap for the future research in this area.

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BMP-treated human embryonic stem cells transcriptionally resemble amnion cells in the monkey embryo

Biology Open ◽

10.1242/bio.058617 ◽

2021 ◽

Author(s):

Sapna Chhabra ◽

Aryeh Warmflash

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Single Cell ◽

Human Embryonic Stem Cells ◽

Inner Cell Mass ◽

Cell Mass ◽

Embryonic Stem ◽

Cell Types ◽

Human Embryos ◽

Early Human

Human embryonic stem cells (hESCs) possess an immense potential to generate clinically relevant cell types and unveil mechanisms underlying early human development. However, using hESCs for discovery or translation requires accurately identifying differentiated cell types through comparison with their in vivo counterparts. Here, we set out to determine the identity of much debated BMP-treated hESCs by comparing their transcriptome to recently published single cell transcriptomic data from early human embryos (Xiang et al., 2019). Our analyses reveal several discrepancies in the published human embryo dataset, including misclassification of putative amnion, intermediate and inner cell mass cells. These misclassifications primarily resulted from similarities in pseudogene expression, highlighting the need to carefully consider gene lists when making comparisons between cell types. In the absence of a relevant human dataset, we utilized the recently published single cell transcriptome of the early post implantation monkey embryo to discern the identity of BMP-treated hESCs. Our results suggest that BMP-treated hESCs are transcriptionally more similar to amnion cells than trophectoderm cells in the monkey embryo. Together with prior studies, this result indicates that hESCs possess a unique ability to form mature trophectoderm subtypes via an amnion-like transcriptional state.

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The derivation and potential use of human embryonic stem cells

Reproduction Fertility and Development ◽

10.1071/rd01101 ◽

2001 ◽

Vol 13 (8) ◽

pp. 523 ◽

Cited By ~ 28

Author(s):

Alan O. Trounson

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Regenerative Medicine ◽

Human Embryonic Stem Cells ◽

High Efficiency ◽

Es Cells ◽

Cell Mass ◽

Embryonic Stem ◽

Cell Types ◽

Specific Cell

Human embryonic stem cells lines can be derived from human blastocysts at high efficiency (>50%) by immunosurgical isolation of the inner cell mass and culture on embryonic fibroblast cell lines. These cells will spontaneously differentiate into all the primary embryonic lineages in vitro and in vivo, but they are unable to form an integrated embryo or body plan by themselves or when combined with trophectoderm cells. They may be directed into a number of specific cell types and this enrichment process requires specific growth factors, cell-surface molecules, matrix molecules and secreted products of other cell types. Embryonic stem (ES) cells are immortal and represent a major potential for cell therapies for regenerative medicine. Their use in transplantation may depend on the formation of a large bank of suitable human leucocyte antigen (HLA) types or the genetic erasure of their HLA expression. Successful transplantation may also require induction of tolerance in recipients and ongoing immune suppression. Although it is possible to customize ES cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation. Embryonic stem cell research may deliver a new pathway for regenerative medicine.

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BMP-treated human embryonic stem cells transcriptionally resemble amnion cells in the monkey embryo

10.1101/2021.01.21.427650 ◽

2021 ◽

Author(s):

Sapna Chhabra ◽

Aryeh Warmflash

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Single Cell ◽

Human Embryonic Stem Cells ◽

Inner Cell Mass ◽

Cell Mass ◽

Embryonic Stem ◽

Cell Types ◽

Human Embryos ◽

Early Human

AbstractHuman embryonic stem cells (hESCs) possess an immense potential to generate clinically relevant cell types and unveil mechanisms underlying early human development. However, using hESCs for discovery or translation requires accurately identifying differentiated cell types through comparison with their in vivo counterparts. Here, we set out to determine the identity of much debated BMP-treated hESCs by comparing their transcriptome to the recently published single cell transcriptomes of early human embryos in the study Xiang et al 2019. Our analyses reveal several discrepancies in the published human embryo dataset, including misclassification of putative amnion, intermediate and inner cell mass cells. These misclassifications primarily resulted from similarities in pseudogene expression, highlighting the need to carefully consider gene lists when making comparisons between cell types. In the absence of a relevant human dataset, we utilized the recently published single cell transcriptome of the early post implantation monkey embryo to discern the identity of BMP-treated hESCs. Our results suggest that BMP-treated hESCs are transcriptionally more similar to amnion cells than trophectoderm cells in the monkey embryo. Together with prior studies, this result indicates that hESCs possess a unique ability to form mature trophectoderm subtypes via an amnion-like transcriptional state.

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Effects of Ionizing Radiation on Self-Renewal and Pluripotency of Human Embryonic Stem Cells

Cancer Research ◽

10.1158/0008-5472.can-09-4238 ◽

2010 ◽

Vol 70 (13) ◽

pp. 5539-5548 ◽

Cited By ~ 56

Author(s):

Kitchener D. Wilson ◽

Ning Sun ◽

Mei Huang ◽

Wendy Y. Zhang ◽

Andrew S. Lee ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Ionizing Radiation ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Self Renewal

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Differentiation of Human Embryonic Stem Cells into Neuron, Cholinergic, and Glial Cells

Stem Cells International ◽

10.1155/2020/8827874 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Kimia Hosseini ◽

Emilia Lekholm ◽

Aikeremu Ahemaiti ◽

Robert Fredriksson

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Glial Cells ◽

Human Embryonic Stem Cells ◽

Inner Cell Mass ◽

Cell Mass ◽

Embryonic Stem ◽

Cholinergic Neurons ◽

Neuronal Cultures ◽

Short Period

Human embryonic stem cells (hESCs) are pluripotent cells, capable of differentiation into different cellular lineages given the opportunity. Derived from the inner cell mass of blastocysts in early embryonic development, the cell self-renewal ability makes them a great tool for regenerative medicine, and there are different protocols available for maintaining hESCs in their undifferentiated state. In addition, protocols for differentiation into functional human neural stem cells (hNSCs), which have the potential for further differentiation into various neural cell types, are available. However, many protocols are time-consuming and complex and do not always fit for purpose. In this study, we carefully combined, optimized, and developed protocols for differentiation of hESCs into adherent monolayer hNSCs over a short period of time, with the possibility of both expansion and freezing. Moreover, the method details further differentiation into neurons, cholinergic neurons, and glial cells in a simple, single step by step protocol. We performed immunocytochemistry, qPCR, and electrophysiology to examine the expression profile and characteristics of the cells to verify cell lineage. Using presented protocols, the creation of neuronal cultures, cholinergic neurons, and a mixed culture of astrocytes and oligodendrocytes can be completed within a three-week time period.

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Expression of pluripotency-associated genes in the surviving fraction of cultured human embryonic stem cells is not significantly affected by ionizing radiation

Gene ◽

10.1016/j.gene.2010.01.006 ◽

2010 ◽

Vol 455 (1-2) ◽

pp. 8-15 ◽

Cited By ~ 25

Author(s):

Mykyta V. Sokolov ◽

Irina V. Panyutin ◽

Mykola I. Onyshchenko ◽

Igor G. Panyutin ◽

Ronald D. Neumann

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Ionizing Radiation ◽

Human Embryonic Stem Cells ◽

Embryonic Stem

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Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation

International Journal of Molecular Sciences ◽

10.3390/ijms21239052 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9052

Author(s):

Indrek Teino ◽

Antti Matvere ◽

Martin Pook ◽

Inge Varik ◽

Laura Pajusaar ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Target Genes ◽

Expression Patterns ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Cell Types ◽

Early Differentiation

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.

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