scholarly journals Generation of male differentiated germ cells from various types of stem cells

Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. R179-R188 ◽  
Author(s):  
Jingmei Hou ◽  
Shi Yang ◽  
Hao Yang ◽  
Yang Liu ◽  
Yun Liu ◽  
...  

Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10–15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells ‘especially functional spermatids’ is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients.

2012 ◽  
Vol 14 (4) ◽  
pp. 574-579 ◽  
Author(s):  
Yong Zhu ◽  
Hong-Liang Hu ◽  
Peng Li ◽  
Shi Yang ◽  
Wei Zhang ◽  
...  

Author(s):  
Na Zhao ◽  
Min Sheng ◽  
Xia Wang ◽  
Yonghui Li ◽  
Maryam Farzaneh

: Infertility is defined as not being able to become pregnant or to conceive a child after one year or longer of regular unprotected intercourse. Male infertility refers to a male's inability to cause pregnancy that can result from deficiencies in semen quality, sperm concentration, or abnormal sperm function. Till now, there are few effective methods for the treatment of a couple with male infertility. In the past few years, stem cell-based therapy as a promising strategy has emerged for the treatment of male infertility. Human pluripotent stem cells (hPSCs) can self-renew and differentiate into any type of cell. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are two pluripotent populations that can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. Both undifferentiated hiPSCs and hESCs are powerful candidates for the treatment of male infertility. Generation of male germ cells from hPSCs can provide new mechanistic insights into the regulation of spermatogenesis and have a great opportunity to families with infertility. Therefore, a robust, reproducible, and low-cost culture method that supports hPSCs differentiation into male germ cells is necessary. However, very few studies have focused on the derivation of sperm-like cells from hiPSCs and the details of hPSCs differentiation into male germ cells have not been fully investigated. Therefore, in this review, we focus on the in vitro differentiation potential of hiPSCs into male germ cells.


2018 ◽  
Author(s):  
Christopher L. Baker ◽  
Michael Walker ◽  
Seda Arat ◽  
Guruprasad Ananda ◽  
Pavlina Petkova ◽  
...  

ABSTRACTAlthough a variety of writers, readers, and erasers of epigenetic modifications are known, we have little information about the underlying regulatory systems controlling the establishment and maintenance of the epigenetic landscape, which varies greatly among cell types. Here, we have explored how natural genetic variation impacts the epigenome in mice. Studying levels of H3K4me3, a histone modification at sites such as promoters, enhancers, and recombination hotspots, we found tissue-specific trans-regulation of H3K4me3 levels in four highly diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. To identify the genetic loci involved, we measured H3K4me3 levels in male germ cells in a mapping population of 60 BXD recombinant inbred lines, identifying extensive trans-regulation primarily controlled by six major histone quantitative trait loci (hQTL). These chromatin regulatory loci act dominantly to suppress H3K4me3, which at hotspots reduces the likelihood of subsequent DNA double-strand breaks. QTL locations do not correspond with enzyme known to metabolize chromatin features. Instead their locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, tissue-specific set of chromatin regulatory loci that control functionally related chromatin sites.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Veronica Ramirez ◽  
Prasanna Krishnamurthy ◽  
Suresh Verma ◽  
...  

Cardiomyocytes derived from embryonic and induced pluripotent stem cells (ES/iPS) provide an excellent source for cell replacement therapies following myocardial ischemia. However, some of the obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their cardiovascular specific differentiation. We identified Histone Deacetylase 1 (HDAC1) as a crucial regulator in early differentiation of mES and iPS cells. We propose a novel pathway in which HDAC1 regulates cardiovascular differentiation by regulating SOX17 which in turn regulates BMP2 signaling in differentiating pluripotent cells. Utilizing stable HDAC1 knock-down (HDAC1-KD) cell lines, we report an essential role for HDAC1 in deacetylating regulatory regions of pluripotency-associated genes during early cardiovascular differentiation. HDAC1-KD cells show severely repressed cardiomyocyte differentiation potential. We propose a novel HDAC1-BMP2-SOX17 dependent pathway through which deacetylation of pluripotency associated genes leads to their suppression and allows for early cardiovascular-associated genes to be expressed and differentiation to occur. Furthermore, we show that HDAC1 affects DNA methylation both during pluripotency and differentiation and plays a crucial, non-redundant role in cardiovascular specific differentiation and cardiomyocyte maturation. Our data elucidates important differences between ES and iPS HDAC1-KD cells that affect their ability to differentiate into cardiovascular lineages. As varying levels of chromatin modifying enzymes are likely to exist in patient derived iPS cells, understanding the molecular circuitry of these enzymes in ES and iPS cells is critical for their potential therapeutic applications in regenerative medicine. Further research in the molecular mechanisms involved in this process will greatly aid our understanding of the epigenetic circuitry of pluripotency and differentiation in pluripotent cells.


2021 ◽  
pp. 75-89
Author(s):  
Jonathan Slack

‘Tissue-specific stem cells’ explores tissue-specific stem cells, which are stem cells found in the postnatal body that are responsible for tissue renewal or for repair following damage. Tissue-specific stem cells share with pluripotent stem cells the same ability to persist indefinitely as a population, to reproduce themselves, and to generate differentiated progeny cells. However, tissue-specific stem cells share few molecular characteristics with embryonic stem (ES) cells or induced pluripotent stem cells (iPS cells), such as expression of specific transcription factors or cell surface molecules. Only renewal tissues have stem cells in the sense of a special population of cells that reproduce themselves and continue to generate differentiated progeny.


2020 ◽  
Vol 21 (15) ◽  
pp. 5467
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Cynthia Machado Cascabulho ◽  
Luiz Anastácio Alves ◽  
Andrea Henriques-Pons

Induced pluripotent stem (iPS) cells are laboratory-produced cells that combine the biological advantages of somatic adult and stem cells for cell-based therapy. The reprogramming of cells, such as fibroblasts, to an embryonic stem cell-like state is done by the ectopic expression of transcription factors responsible for generating embryonic stem cell properties. These primary factors are octamer-binding transcription factor 4 (Oct3/4), sex-determining region Y-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and the proto-oncogene protein homolog of avian myelocytomatosis (c-Myc). The somatic cells can be easily obtained from the patient who will be subjected to cellular therapy and be reprogrammed to acquire the necessary high plasticity of embryonic stem cells. These cells have no ethical limitations involved, as in the case of embryonic stem cells, and display minimal immunological rejection risks after transplant. Currently, several clinical trials are in progress, most of them in phase I or II. Still, some inherent risks, such as chromosomal instability, insertional tumors, and teratoma formation, must be overcome to reach full clinical translation. However, with the clinical trials and extensive basic research studying the biology of these cells, a promising future for human cell-based therapies using iPS cells seems to be increasingly clear and close.


2020 ◽  
Vol 114 (3) ◽  
pp. e439
Author(s):  
Sherina Lawrence ◽  
Mounia Haddad ◽  
Philip Xie ◽  
Zev Rosenwaks ◽  
Gianpiero D. Palermo

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