Three-dimensional Genome Structure Reveals Distinct Chromatin Signatures of Mouse Female Germline Stem Cells During Development

SUMMARYThe three-dimensional configuration of the genome ensures cell-type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we revealed the distinct features of the chromatin architecture in female germline stem cells (FGSCs) by in situ high-throughput chromosome conformation analysis. We also showed that the X chromosome structures were similar in spermatogonial stem cells and FGSCs. Using integrative analysis of the three-dimensional chromatin structure, we observed that the TADs were attenuated in germinal vesicle oocytes and disappeared in metaphase II oocytes during FGSC development. Finally, we identified conserved compartments belonging to the paternal/maternal genomes during early embryonic development, which were related to imprinted genes. These results will provide a valuable resource for studying and further our understanding of the fundamental characteristics of oogenesis and early embryo development.

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Integrative analysis of the 3D genome structure reveals that CTCF maintains the properties of mouse female germline stem cells

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-04107-y ◽

2022 ◽

Vol 79 (1) ◽

Author(s):

Geng G. Tian ◽

Xinyan Zhao ◽

Changliang Hou ◽

Wenhai Xie ◽

Xiaoyong Li ◽

...

Keyword(s):

Stem Cells ◽

Chromatin Structure ◽

Three Dimensional ◽

High Order ◽

Chromatin Organization ◽

Germline Stem Cells ◽

High Order Chromatin Structure ◽

Female Germline ◽

High Order Chromatin

AbstractThe three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we used in situ high-throughput chromosome conformation (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to characterize the high-order chromatin structure signature of female germline stem cells (FGSCs) and identify its regulating key factor based on the data-driven of multiple omics data. By comparison with pluripotent stem cells (PSCs), adult stem cells (ASCs), and somatic cells at three major levels of chromatin architecture, A/B compartments, topologically associating domains, and chromatin loops, the chromatin architecture of FGSCs was most similar to that of other ASCs and largely different from that of PSCs and somatic cells. After integrative analysis of the three-dimensional chromatin structure, active compartment-associating loops (aCALs) were identified as a signature of high-order chromatin organization in FGSCs, which revealed that CCCTC-binding factor was a major factor to maintain the properties of FGSCs through regulation of aCALs. We found FGSCs belong to ASCs at chromatin structure level and characterized aCALs as the high-order chromatin structure signature of FGSCs. Furthermore, CTCF was identified to play a key role in regulating aCALS to maintain the biological functions of FGSCs. These data provide a valuable resource for future studies of the features of chromatin organization in mammalian stem cells and further understanding of the fundamental characteristics of FGSCs.

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Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

The International Journal of Artificial Organs ◽

10.1177/0391398820986809 ◽

2021 ◽

pp. 039139882098680

Author(s):

Xuefeng Zhang ◽

Nan Wang ◽

Yuhua Huang ◽

Yan Li ◽

Gang Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Therapeutic Potential ◽

Expression Profiles ◽

Ischemia Reperfusion ◽

Three Dimensional ◽

3D Culture ◽

Placental Mesenchymal Stem Cells ◽

2D And 3D

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.

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Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

Stem Cells International ◽

10.1155/2017/6072406 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Gayathri Subramanian ◽

Alexander Stasuk ◽

Mostafa Elsaadany ◽

Eda Yildirim-Ayan

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Expression Profiles ◽

Three Dimensional ◽

Uniaxial Tensile ◽

Adipose Derived Stem Cells ◽

Collagen Scaffolds ◽

Differentiation Potential ◽

Tenogenic Differentiation ◽

Matrix Organization

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

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How Can Female Germline Stem Cells Contribute to the Physiological Neo-Oogenesis in Mammals and Why Menopause Occurs?

Microscopy and Microanalysis ◽

10.1017/s143192761000036x ◽

2010 ◽

Vol 17 (4) ◽

pp. 498-505 ◽

Cited By ~ 11

Author(s):

Antonin Bukovsky

Keyword(s):

Stem Cells ◽

Adult Mouse ◽

Mammalian Species ◽

Reproductive Period ◽

Germline Stem Cells ◽

Environmental Threats ◽

Ovarian Stem Cells ◽

Lower Vertebrates ◽

Female Germline ◽

Prevailing View

AbstractAt the beginning of the last century, reproductive biologists have discussed whether in mammalian species the fetal oocytes persist or are replaced by neo-oogenesis during adulthood. Currently the prevailing view is that neo-oogenesis is functional in lower vertebrates but not in mammalian species. However, contrary to the evolutionary rules, this suggests that females of lower vertebrates have a better opportunity to provide healthy offspring compared to mammals with oocytes subjected to environmental threats for up to several decades. During the last 15 years, a new effort has been made to determine whether the oocyte pool in adult mammals is renewed as well. Most recently, Ji Wu and colleagues reported a production of offspring from female germline stem cells derived from neonatal and adult mouse ovaries. This indicates that both neonatal and adult mouse ovaries carry stem cells capable of producing functional oocytes. However, it is unclear whether neo-oogenesis from ovarian somatic stem cells is physiologically involved in follicular renewal and why menopause occurs. Here we review observations that indicate an involvement of immunoregulation in physiological neo-oogenesis and follicular renewal from ovarian stem cells during the prime reproductive period and propose why menopause occurs in spite of persisting ovarian stem cells.

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GSK3 inhibitor-BIO regulates proliferation of female germline stem cells from the postnatal mouse ovary

Cell Proliferation ◽

10.1111/j.1365-2184.2012.00821.x ◽

2012 ◽

Vol 45 (4) ◽

pp. 287-298 ◽

Cited By ~ 20

Author(s):

Y. Hu ◽

Y. Bai ◽

Z. Chu ◽

J. Wang ◽

L. Wang ◽

...

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Mouse Ovary ◽

Female Germline ◽

Gsk3 Inhibitor

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A new tool to generate transgenic rats using female germline stem cells from post-natal ovaries

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gau017 ◽

2014 ◽

Vol 20 (4) ◽

pp. 283-285 ◽

Cited By ~ 5

Author(s):

Y. Pan

Keyword(s):

Stem Cells ◽

Germline Stem Cells ◽

Transgenic Rats ◽

Female Germline

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Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation

Science Advances ◽

10.1126/sciadv.aav8550 ◽

2018 ◽

Vol 4 (12) ◽

pp. eaav8550 ◽

Cited By ~ 12

Author(s):

Suhn K. Rhie ◽

Shannon Schreiner ◽

Heather Witt ◽

Chris Armoskus ◽

Fides D. Lay ◽

...

Keyword(s):

Cell Model ◽

Expression Profiles ◽

Neuronal Cells ◽

Three Dimensional ◽

Gene Expression Profiles ◽

Regulatory Elements ◽

A Genome ◽

Wide Scale ◽

Cell Model System ◽

Distal Regulatory Elements

As part of PsychENCODE, we developed a three-dimensional (3D) epigenomic map of primary cultured neuronal cells derived from olfactory neuroepithelium (CNON). We mapped topologically associating domains and high-resolution chromatin interactions using Hi-C and identified regulatory elements using chromatin immunoprecipitation and nucleosome positioning assays. Using epigenomic datasets from biopsies of 63 living individuals, we found that epigenetic marks at distal regulatory elements are more variable than marks at proximal regulatory elements. By integrating genotype and metadata, we identified enhancers that have different levels corresponding to differences in genetic variation, gender, smoking, and schizophrenia. Motif searches revealed that many CNON enhancers are bound by neuronal-related transcription factors. Last, we combined 3D epigenomic maps and gene expression profiles to predict enhancer-target gene interactions on a genome-wide scale. This study not only provides a framework for understanding individual epigenetic variation using a primary cell model system but also contributes valuable data resources for epigenomic studies of neuronal epithelium.

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