Project description:Np63+ve cells are multipotent and maintain all epithelial cell lineages of the embryonic and adult salivary gland (SG). However, the molecular mechanisms by which Np63 regulates stem/progenitor (SP) cell populations in the SG remains elusive. To better understand Np63 s role in directing cell fate choices, here we have utilized Np63-null adult mice and primary salivary cell cultures to probe alterations in SP cell differentiation and function. Specifically, we have generated bulk RNA-seq and scRNA-seq data from Np63-null adult mice and p63 and H3K27Ac ChIP-seq data from primary salivary cell cultures. These genomic and epigenomic data sets were leveraged to interrogate altered SG cellular identities and differentiation states resulting from the loss of Np63. Our studies reveal that ablation of Np63 results in a loss of the SP cell population and skewed SG differentiation that is modulated by dysregulated TGF- /Activin signaling. Our findings offer new molecular revelations into the SP cell gene regulatory networks that are likely to be relevant for normal or diseased SG states.
Project description:Np63+ve cells are multipotent and maintain all epithelial cell lineages of the embryonic and adult salivary gland (SG). However, the molecular mechanisms by which Np63 regulates stem/progenitor (SP) cell populations in the SG remains elusive. To better understand Np63 s role in directing cell fate choices, here we have utilized Np63-null adult mice and primary salivary cell cultures to probe alterations in SP cell differentiation and function. Specifically, we have generated bulk RNA-seq and scRNA-seq data from Np63-null adult mice and p63 and H3K27Ac ChIP-seq data from primary salivary cell cultures. These genomic and epigenomic data sets were leveraged to interrogate altered SG cellular identities and differentiation states resulting from the loss of Np63. Our studies reveal that ablation of Np63 results in a loss of the SP cell population and skewed SG differentiation that is modulated by dysregulated TGF- /Activin signaling. Our findings offer new molecular revelations into the SP cell gene regulatory networks that are likely to be relevant for normal or diseased SG states.
Project description:Np63+ve cells are multipotent and maintain all epithelial cell lineages of the embryonic and adult salivary gland (SG). However, the molecular mechanisms by which Np63 regulates stem/progenitor (SP) cell populations in the SG remains elusive. To better understand Np63 s role in directing cell fate choices, here we have utilized Np63-null adult mice and primary salivary cell cultures to probe alterations in SP cell differentiation and function. Specifically, we have generated bulk RNA-seq and scRNA-seq data from Np63-null adult mice and p63 and H3K27Ac ChIP-seq data from primary salivary cell cultures. These genomic and epigenomic data sets were leveraged to interrogate altered SG cellular identities and differentiation states resulting from the loss of Np63. Our studies reveal that ablation of Np63 results in a loss of the SP cell population and skewed SG differentiation that is modulated by dysregulated TGF- /Activin signaling. Our findings offer new molecular revelations into the SP cell gene regulatory networks that are likely to be relevant for normal or diseased SG states.
Project description:Adult stem cell activity and organ development are elaborately regulated by microenvironmental signals. However, little is known about the regulatory effects of microenvironmental sympathetic nerve signals on organ development and stem cell activity. Here, using a mouse mammary gland model, we determined the regulatory function of sympathetic nerve system (SNS) on mammary development and mammary stem cell activity. Our results indicated that depletion of sympathetic nerve signals delayed the elongation of mammary ducts during puberty and pregnancy, and lead to the loss of mammary stem cells (MaSCs). In vitro three-dimensional (3D) culture and in vivo transplantation analyses indicated that the loss of sympathetic nerve signals inhibits the self-renewal and reconstruction activity of mammary stem cells, while the activation of sympathetic nerve signals promotes the self-renewal and reconstruction activity of mammary stem cells. Mechanistically, we found that sympathetic nerve signals regulate the activity of mammary stem cells and mammary development through the PI3K/ERK pathway. Together, our study reveals the function of sympathetic nervous signals in maintaining mammary homeostasis and regulating mammary stem cell activity, providing a novel view for the nervous system's regulation of organ development.
