Progression from a stem cell-like state to early differentiation in the C. elegans germ line.
Controls of stem cell maintenance and early differentiation are known in several systems. However, the progression from stem cell self-renewal to overt signs of early differentiation is a poorly understood but important problem in stem cell biology. The Caenorhabditis elegans germ line provides a genetically defined model for studying that progression. In this system, a single-celled mesenchymal niche, the distal tip cell (DTC), employs GLP-1/Notch signaling and an RNA regulatory network to balance self-renewal and early differentiation within the "mitotic region," which continuously self-renews while generating new gametes. Here, we investigate germ cells in the mitotic region for their capacity to differentiate and their state of maturation. Two distinct pools emerge. The "distal pool" is maintained by the DTC in an essentially uniform and immature or "stem cell-like" state; the "proximal pool," by contrast, contains cells that are maturing toward early differentiation and are likely transit-amplifying cells. A rough estimate of pool sizes is 30-70 germ cells in the distal immature pool and approximately 150 in the proximal transit-amplifying pool. We present a simple model for how the network underlying the switch between self-renewal and early differentiation may be acting in these two pools. According to our model, the self-renewal mode of the network maintains the distal pool in an immature state, whereas the transition between self-renewal and early differentiation modes of the network underlies the graded maturation of germ cells in the proximal pool. We discuss implications of this model for controls of stem cells more broadly.
Cinquin
Olivier
O
Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA. ocinquin@uci.edu
Crittenden
Sarah L
SL
Morgan
Dyan E
DE
Kimble
Judith
J
D000818:Animals; D064192:Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature
D064192:Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C094448:GLD-1 protein, C elegans; C060620:Glp-1 protein, C elegans; C121599:HIM-3 protein, C elegans; D008562:Membrane Glycoproteins; D051880:Receptors, Notch