Defects related to maintaining a balance between stem cell renewal and differentiation are associated with several disease conditions such as cancer, diabetes and various neurodegenerative disorders.
there is a keen interest in understanding the mechanisms underlying stem cell specification, maintenance and asymmetric cell division.
Over the course of development, two types of adult stem cells are specified: germline stem cells (GSCs) and somatic stem cells (SSCs).
CELL-EXTRINSIC FACTORS REGULATING STEM CELL FATE
In the context of a tissue, adult stem cells reside in a special microenvironment referred to as the niche
The niche allows interaction between the stem cells and different cell-extrinsic signals. In some instances, these signals are mediated via direct cell-to-cell communication or cell-to-matrix interaction.
the binding of BMP signals by the GSCs outside the niche is controlled by multiple mechanisms.
The asymmetric cell divisions of both the male and female GSCs are regulated via coordination between non-autonomous signaling from the niche and cell-autonomous influences in the form of stem cell-intrinsic factors.
Remarkably, transcription of bam is activated only one cell diameter away from the GSCs, which involves the establishment of a steep gradient of BMP signaling in the niche. Mechanisms that regulate the establishment of this BMP signaling gradient in the niche are not completely understood.
In this regard, it is noteworthy that the components of the extracellular matrix also play a role in maintaining GSC identity.
the binding of BMP signals by the GSCs outside the niche is controlled by multiple mechanisms.
CELL-INTRINSIC DETERMINATION OF STEM CELL FATE
In addition to non-autonomous signaling, cell-autonomous intrinsic factors significantly contribute to the establishment and/or maintenance of stem cell identity and the cells’ subsequent development.
the unique participation of centrosomes in the determination of stem cell fate.
male GSCs retain the mother centrosome, which remains closely anchored to the GSC-hub interface. By contrast, the daughter cell inherits the newly synthesized centrosome and undergoes differentiation. This asymmetric segregation of centrosomes is critical for proper positioning of the spindle and for subsequent spindle orientation with reference to the hub. Importantly, it precedes the asymmetric division of the GSCs, implying their critical role for this asymmetric segregation.
It is unclear, however, whether the non-autonomous signaling and cell-intrinsic transcriptional regulators coordinately control the duplication and uneven separation of the centrosomes among the daughter cells. Furthermore, it remains to be determined whether centrosome assembly and the emanating microtubule network can also modulate the signaling machinery via a feedback mechanism.
although most stem cells need the niche environment for self-renewal and to initiate asymmetric cell division, it is not essential in all contexts.
Epigenetic regulation of adult GSCs in Drosophila
Despite their identical genomic sequence, adult stem cells and differentiated cells possess distinct chromatin structure and gene expression profiles, which are imparted, in part, by epigenetic modifications.
While specific histone modifications serve as indicators of gene activity, the precise mechanisms underlying their mode of action during the acquisition of unique functional traits of stem cells and their differentiating progeny remain to be determined
it is noteworthy that the protein components thought to be involved in chromatin remodeling appear to act in conjunction with the proteins/enzymes involved in epigenetic modifications
Recent work also provides evidence for the role of multiple noncoding RNAs, including piRNAs, in the maintenance of stem cell identity in Drosophila.
Intriguingly, the functional involvement of histones and epigenetic mechanisms in cell fate determination poses an obvious challenge regarding the mechanisms employed to modulate the different epigenetic marks and their distribution during DNA replication.
The functional relationship between the two asymmetry-generating events, however, is uncertain at present
it is of considerable interest to understand how the individual epigenetic marks are inherited differentially during symmetric and asymmetric divisions of adult stem cells.
Common Design 