Cellular differentiation

About: Cellular differentiation is a research topic. Over the lifetime, 90966 publications have been published within this topic receiving 6099252 citations. The topic is also known as: Cellular differentiation & GO:0030154.

Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation

Abstract: The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer. To gain insight into the role of Gata-3 in breast epithelial development and oncogenesis, we have explored its normal function within the mammary gland by conditionally deleting Gata-3 at different stages of development. We report that Gata-3 has essential roles in the morphogenesis of the mammary gland in both the embryo and adult. Through the discovery of a novel marker (beta3-integrin) of luminal progenitor cells and their purification, we demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors and a concomitant block in differentiation. Remarkably, introduction of Gata-3 into a stem cell-enriched population induced maturation along the alveolar luminal lineage. These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation.

Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors

Abstract: The location and timing of cellular differentiation must be stringently controlled for proper organ formation. Normally, hepatocytes differentiate from hepatic progenitor cells to form the liver during development. However, previous studies have shown that the hepatic program can also be activated in non-hepatic lineage cells after exposure to particular stimuli or fusion with hepatocytes. These unexpected findings suggest that factors critical to hepatocyte differentiation exist and become activated to induce hepatocyte-specific properties in different cell types. Here, by screening the effects of twelve candidate factors, we identify three specific combinations of two transcription factors, comprising Hnf4α plus Foxa1, Foxa2 or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells that closely resemble hepatocytes in vitro. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific features and reconstitute damaged hepatic tissues after transplantation. The generation of iHep cells may provide insights into the molecular nature of hepatocyte differentiation and potential therapies for liver diseases.

A skin microRNA promotes differentiation by repressing ‘stemness’

Abstract: In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer. As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme. Here, we show that microRNA-203 is induced in the skin concomitantly with stratification and differentiation. By altering miR-203's spatiotemporal expression in vivo, we show that miR-203 promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit. We identify p63 as one of the conserved targets of miR-203 across vertebrates. Notably, p63 is an essential regulator of stem-cell maintenance in stratified epithelial tissues. We show that miR-203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR-203 is absent and it becomes repressed basally when miR-203 is prematurely expressed. Our findings suggest that miR-203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.