Cellular fate of intersex differentiation

AbstractInfertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. We provide an overview of cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by degradation of female germline cells via liquid–liquid phase separation of the proteasomes in the nucleus, and impaired histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germlines synergistically determined distinct cell fate of both male and female germlines. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation direction of ovotestis, and provide novel insights into ovotestis development.

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Asymmetric histone inheritance regulates stem cell fate in Drosophila midgut

10.1101/2020.08.15.252403 ◽

2020 ◽

Author(s):

Emily Zion ◽

Xin Chen

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Biological Significance ◽

Cell Lineage ◽

Germline Stem Cells ◽

Cell Fates ◽

Stem Cell Fate ◽

Distinct Cell

AbstractA fundamental question in developmental biology is how distinct cell fates are established and maintained through epigenetic mechanisms in multicellular organisms. Here, we report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically inherited by the distinct daughter cells during asymmetric division of Drosophila intestinal stem cells (ISCs). By contrast, in symmetrically dividing ISCs that produce two self-renewed stem cells, old and new H3 and H4 show symmetric inheritance patterns. These results indicate that asymmetric histone inheritance is tightly associated with the distinct daughter cell fates. To further understand the biological significance of this asymmetry, we express a mutant histone that compromises asymmetric histone inheritance pattern. We find increased symmetric ISC division and ISC tumors during aging under this condition. Together, our results demonstrate that asymmetric histone inheritance is important for establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in asymmetrically dividing male germline stem cells in Drosophila. Therefore, this work sheds light on the principles of histone inheritance in regulating stem cell fate in vivo.

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Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells

Development ◽

10.1242/dev.124.18.3651 ◽

1997 ◽

Vol 124 (18) ◽

pp. 3651-3662 ◽

Cited By ~ 8

Author(s):

B. Ohlstein ◽

D. McKearin

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Germ Cell ◽

Cell Fate ◽

Germ Cells ◽

Ectopic Expression ◽

Cell Lineage ◽

Limiting Factor ◽

Germline Stem Cells ◽

Stem Cell Divisions

The Drosophila germ-cell lineage has emerged as a remarkable system for identifying genes required for changes in cell fate from stem cells into more specialized cells. Previous work indicates that bam expression is necessary for cystoblast differentiation; bam mutant germ cells fail to differentiate, but instead proliferate like stem cells. This paper reports that ectopic expression of bam is sufficient to extinguish stem cell divisions. Heat-induced bam+ expression specifically eliminated oogenic stem cells while somatic stem cell populations were not affected. Together with previous studies of the timing of bam mRNA and protein expression and the state of arrest in bam mutant cells, these data implicate Bam as a direct regulator of the switch from stem cell to cystoblast. Surprisingly, ectopic bam+ had no deleterious consequences for male germline cells suggesting that Bam may regulate somewhat different steps of germ-cell development in oogenesis and spermatogenesis. We discuss a model for how bam+ could direct differentiation based on our data (McKearin and Ohlstein, 1995) that Bam protein is essential to assemble part of the germ-cell-specific organelle, the fusome. We propose that fusome biogenesis is an obligate step for cystoblast cell fate and that Bam is the limiting factor for fusome maturation in female germ cells.

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Centromere assembly and non-random sister chromatid segregation in stem cells

Essays in Biochemistry ◽

10.1042/ebc20190066 ◽

2020 ◽

Vol 64 (2) ◽

pp. 223-232 ◽

Cited By ~ 1

Author(s):

Ben L. Carty ◽

Elaine M. Dunleavy

Keyword(s):

Stem Cells ◽

Cell Division ◽

Cell Fate ◽

Sister Chromatid ◽

Asymmetric Cell Division ◽

Protein A ◽

Germline Stem Cells ◽

Sister Chromatids ◽

Centromere Protein A ◽

Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

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Faculty Opinions recommendation of Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice.

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

10.3410/f.725255586.793504217 ◽

2015 ◽

Author(s):

Keith Jones ◽

Guillaume Halet

Keyword(s):

Stem Cells ◽

Cell Lineage ◽

Lineage Tracing ◽

Germline Stem Cells ◽

Adult Mice

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EBF1 is expressed in pericytes and contributes to pericyte cell commitment

Histochemistry and Cell Biology ◽

10.1007/s00418-021-02015-7 ◽

2021 ◽

Author(s):

Francesca Pagani ◽

Elisa Tratta ◽

Patrizia Dell’Era ◽

Manuela Cominelli ◽

Pietro Luigi Poliani

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

B Cell ◽

Cell Fate ◽

Early Stage ◽

Cell Lineage ◽

Cell Maturation ◽

Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

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Functions of promyelocytic leukaemia zinc finger (Plzf) in male germline stem cell development and differentiation

Reproduction Fertility and Development ◽

10.1071/rd18252 ◽

2019 ◽

Vol 31 (8) ◽

pp. 1315 ◽

Cited By ~ 1

Author(s):

Daguia Zambe John Clotaire ◽

Yudong Wei ◽

Xiuwei Yu ◽

Tamgue Ousman ◽

Jinlian Hua

Keyword(s):

Stem Cells ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Development Stage ◽

Cell Development ◽

Promyelocytic Leukaemia ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

Male Germline ◽

Finger Protein

Promyelocytic leukaemia zinc finger (Plzf), also known as zinc finger and BTB domain containing 16 (ZBTB16) or zinc-finger protein 145 (ZFP145), is a critical zinc finger protein of male germline stem cells (mGSCs). Multiple lines of evidence indicate that Plzf has a central role in the development, differentiation and maintenance of many stem cells, including mGSCs, and Plzf has been validated as an essential transcription factor for mammalian testis development and spermatogenesis. This review summarises current literature focusing on the significance of Plzf in maintaining and regulating self-renewal and differentiation of mGSCs, especially goat mGSCs. The review summarises evidence of the specificity of Plzf expression in germ cell development stage, the known functions of Plzf and the microRNA-mediated mechanisms that control Plzf expression in mGSCs.

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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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