The phenomenon of diverse families has expanded in recent years. Although it has important implications in the field of education, this issue has been largely overlooked in the research on early ...education in Israel. The aim of the present study is to examine the attitudes of Israeli kindergarten teachers towards diverse families and the practices they use in this context. For this purpose, we conducted a qualitative study, using in-depth, semi-structured interviews among 20 Jewish-Israeli state kindergarten teachers. The main findings are that, overall, the attitudes of kindergarten teachers towards diverse families are positive, and they use different practices for dealing with family diversity and integrate this issue in their routine educational activities. Despite this, due to various factors, the positive attitudes are not always implemented in practice. These findings highlight the need to guide kindergarten teachers to work with diverse families, preparing them to adapt to the changing society.
Primary liver cancers include hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA) and combined HCC-CCA tumors (cHCC-CCA). It has been suggested, but not unequivocally proven, that ...hepatic progenitor cells (HPCs) can contribute to hepatocarcinogenesis. We aimed to determine whether HPCs contribute to HCC, cHCC-CCA or both types of tumors.
To trace progenitor cells during hepatocarcinogenesis, we generated Mdr2-KO mice that harbor a yellow fluorescent protein (YFP) reporter gene driven by the Foxl1 promoter which is expressed specifically in progenitor cells. These mice (Mdr2-KOFoxl1-CRE;RosaYFP) develop chronic inflammation and HCCs by the age of 14-16 months, followed by cHCC-CCA tumors at the age of 18 months.
In this Mdr2-KOFoxl1-CRE;RosaYFP mouse model, liver progenitor cells are the source of cHCC-CCA tumors, but not the source of HCC. Ablating the progenitors, caused reduction of cHCC-CCA tumors but did not affect HCCs. RNA-sequencing revealed enrichment of the IL-6 signaling pathway in cHCC-CCA tumors compared to HCC tumors. Single-cell RNA-sequencing (scRNA-seq) analysis revealed that IL-6 is expressed by immune and parenchymal cells during senescence, and that IL-6 is part of the senescence-associated secretory phenotype. Administration of an anti-IL-6 antibody to Mdr2-KOFoxl1-CRE;RosaYFP mice inhibited the development of cHCC-CCA tumors. Blocking IL-6 trans-signaling led to a decrease in the number and size of cHCC-CCA tumors, indicating their dependence on this pathway. Furthermore, the administration of a senolytic agent inhibited IL-6 and the development of cHCC-CCA tumors.
Our results demonstrate that cHCC-CCA, but not HCC tumors, originate from HPCs, and that IL-6, which derives in part from cells in senescence, plays an important role in this process via IL-6 trans-signaling. These findings could be applied to develop new therapeutic approaches for cHCC-CCA tumors.
Combined hepatocellular carcinoma–cholangiocarcinoma is the third most prevalent type of primary liver cancer (i.e. a cancer that originates in the liver). Herein, we show that this type of cancer originates in stem cells in the liver and that it depends on inflammatory signaling. Specifically, we identify a cytokine called IL-6 that appears to be important in the development of these tumors. Our results could be used for the development of novel treatments for these aggressive tumors.
Display omitted
•The combined HCC-CCA tumor originates from hepatic progenitors.•Hepatic progenitors are not the source of HCC.•Combined HCC-CCA initiate on the background of liver inflammation.•Combined HCC-CCA development is dependent on IL-6 trans-signaling.•Senescence contributes to combined HCC-CCA development through IL-6 secretion.
