Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor‐Marked Stromal Population from Adipogenic to Osteoblastic Lineage

2019 ◽  
Vol 34 (10) ◽  
pp. 1952-1963 ◽  
Author(s):  
Mengyu Yang ◽  
Atsushi Arai ◽  
Nobuyuki Udagawa ◽  
Lijuan Zhao ◽  
Daisuke Nishida ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Fate ◽  
Leptin Receptor ◽  
Osteoblastic Lineage

Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 513-525 ◽  
Author(s):  
J. Foley ◽  
P. Dann ◽  
J. Hong ◽  
J. Cosgrove ◽  
B. Dreyer ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Mesenchymal Cells ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Mammary Mesenchyme ◽  
Pthrp Receptor

Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and (β)-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.

scholarly journals Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor‐Positive Pericyte Network in Mice

2019 ◽  
Vol 34 (8) ◽  
pp. 1487-1501 ◽  
Author(s):  
Robin Caire ◽  
Bernard Roche ◽  
Tiphanie Picot ◽  
Carmen‐Mariana Aanei ◽  
Zhiguo He ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Leptin Receptor

scholarly journals Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate

2017 ◽  
Vol 25 (3) ◽  
pp. 661-672 ◽  
Author(s):  
Yi Fan ◽  
Jun-ichi Hanai ◽  
Phuong T. Le ◽  
Ruiye Bi ◽  
David Maridas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Parathyroid Hormone ◽  
Cell Fate ◽  
Mesenchymal Cell ◽  
Bone Marrow Mesenchymal Cell

scholarly journals The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin

2021 ◽  
Vol 118 (25) ◽  
pp. e2026176118
Author(s):  
Jingzhu Zhang ◽  
Adi Cohen ◽  
Bo Shen ◽  
Liming Du ◽  
Alpaslan Tasdogan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Parathyroid Hormone ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Wnt Pathway ◽  
Leptin Receptor ◽  
Marrow Stromal Cells ◽  
Pathway Activation ◽  
Osteogenic Response

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor+ (LepR+) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.

LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration

2020 ◽  
Vol 99 (11) ◽  
pp. 1279-1286 ◽  
Author(s):  
D. Zhang ◽  
S. Zhang ◽  
J. Wang ◽  
Q. Li ◽  
H. Xue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Parathyroid Hormone ◽  
Bone Regeneration ◽  
Cell Population ◽  
Leptin Receptor ◽  
Alveolar Bone ◽  
Critical Role ◽  
Long Bone ◽  
Stem Cell Population ◽  
Genetic Ablation

Stem cells play a critical role in bone regeneration. Multiple populations of skeletal stem cells have been identified in long bone, while their identity and functions in alveolar bone remain unclear. Here, we identified a quiescent leptin receptor–expressing (LepR+) cell population that contributed to intramembranous bone formation. Interestingly, these LepR+ cells became activated in response to tooth extraction and generated the majority of the newly formed bone in extraction sockets. In addition, genetic ablation of LepR+ cells attenuated extraction socket healing. The parabiosis experiments revealed that the LepR+ cells in the healing sockets were derived from resident tissue rather than peripheral blood circulation. Further studies on the mechanism suggested that these LepR+ cells were responsive to parathyroid hormone/parathyroid hormone 1 receptor (PTH/PTH1R) signaling. Collectively, we demonstrate that LepR+ cells, a postnatal skeletal stem cell population, are essential for alveolar bone regeneration of extraction sockets.

Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3485-3493
Author(s):  
M.E. Dunbar ◽  
P.R. Dann ◽  
G.W. Robinson ◽  
L. Hennighausen ◽  
J.P. Zhang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Fate ◽  
Ectopic Expression ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Cell Fate Decisions ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression ◽  
Mammary Mesenchyme

Male mice lack mammary glands due to the interaction of circulating androgens with local epithelial-mesenchymal signaling in the developing mammary bud. Mammary epithelial cells induce androgen receptor (AR) within the mammary mesenchyme and, in response to androgens, the mesenchyme condenses around the epithelial bud, destroying it. We show that this process involves apoptosis and that, in the absence of parathyroid hormone-related protein (PTHrP) or its receptor, the PTH/PTHrP receptor (PPR1), it fails due to a lack of mesenchymal AR expression. In addition, the expression of tenascin C, another marker of the mammary mesenchyme, is also dependent on PTHrP. PTHrP expression is initiated on E11 and, within the ventral epidermis, is restricted to the forming mammary epithelial bud. In contrast, PPR1 expression is not limited to the mammary bud, but is found generally within the subepidermal mesenchyme. Finally, transgenic overexpression of PTHrP within the basal epidermis induces AR and tenasin C expression within the ventral dermis, suggesting that ectopic expression of PTHrP can induce the ventral mesenchyme to express mammary mesenchyme markers. We propose that PTHrP expression specifically within the developing epithelial bud acts as a dominant signal participating in cell fate decisions leading to a specialized mammary mesenchyme.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

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

2020 ◽  
Vol 64 (2) ◽  
pp. 223-232 ◽  
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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