A key challenge in stem cell research is to learn how to direct the differentiation of stem cells toward specific fates. In this issue of Cell, Engler et al. (2006) identify a new factor regulating stem cell fate: the elasticity of the matrix microenvironment. By changing the stiffness of the substrate, human mesenchymal stem cells could be directed along neuronal, muscle, or bone lineages.

The level of transcription factor activity critically regulates cell fate decisions such as hematopoietic stem cell self-renewal and differentiation. The balance between hematopoietic stem cell self-renewal and differentiation needs to be tightly controlled, as a shift toward differentiation might exhaust the stem cell pool, while a shift toward self-renewal might mark the onset of leukemic tra...

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC) and micro-contact printing (microCP)...

Hematopoietic stem cells (HSCs) are characterized by their ability to self-renew and differentiate into all blood lineage cells. The fate decisions of HSCs (self-renewal versus differentiation) are made through the process of cell division and are often compared to "birth" and "death". Stem cells give rise to undifferentiated stem cells (birth) or differentiate into progenitor cells (death). Th...

Normal steady-state hematopoiesis takes place in the bone marrow microenvironment. Soluble factors as well as contact interactions between the hematopoietic cells and the marrow microenvironment dictate the fate of hematopoietic stem cells and progenitors. Over the last decade it has become clear that cell-cell and cell-extracellular matrix interactions through adhesion receptors play a major r...

Cell fate is determined by intrinsic programs and external cues, such as soluble signals and cell-cell contact. Previous studies have demonstrated the roles of soluble factors in the proliferation and differentiation of cortical stem cells and cell-cell contact in maintaining stem cells in a proliferative state. In the present study, we focused on the effect of cell-cell interaction on cell-fat...

Stem cells have the capability to self-renew and maintain their undifferentiated state or to differentiate into one or more specialised cell types. Stem cell expansion and manipulation ex vivo is a promising approach for engineering cell replacement therapies, and endogenous stem cells represent potential drugable targets for tissue repair. Before we can harness stem cells' therapeutic potentia...

Stem cells possess the properties of self-renewal and differentiation, and mainly rely on two strategies for division, including symmetric and asymmetric cell divisions. In this review, we summarize the latest progress on asymmetric cell divisions in Drosophila melanogaster neuroblasts (NBs), which focus on the establishment of cell polarity, mitotic spindle orientation, the asymmetric segregat...

Physical factors in the local cellular microenvironment, including cell shape and geometry, matrix mechanics, external mechanical forces, and nanotopographical features of the extracellular matrix, can all have strong influences on regulating stem cell fate. Stem cells sense and respond to these insoluble biophysical signals through integrin-mediated adhesions and the force balance between intr...

The root meristem consists of populations of distal and proximal stem cells and an organizing center known as the quiescent center. During embryogenesis, initiation of the root meristem occurs when an asymmetric cell division of the hypophysis forms the distal stem cells and quiescent center. We have identified NO TRANSMITTING TRACT (NTT) and two closely related paralogs as being required for t...