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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Front. Biol.    2015, Vol. 10 Issue (1) : 1-10    https://doi.org/10.1007/s11515-015-1347-1
REVIEW
Analyzing stem cell dynamics: use of cutting edge genetic approaches in model organisms
Gary R. HIME1,*(),Nicole SIDDALL1,Katja HORVAY2,Helen E. ABUD2
1. Department of Anatomy and Neuroscience, University of Melbourne, VIC 3010, Australia
2. Department of Anatomy and Developmental Biology, Monash University, Clayton VIC 3800, Australia
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Abstract

Regeneration of many cell types found in adult organs relies upon the presence of relatively small pools of undifferentiated stem cells. Initial studies that attempted to isolate stem cells and propagate them in vitro have been complemented by analysis of stem cells in their endogenous tissues where they are subject to a variety of regulatory cues. This has been facilitated by the advent of new methods for lineage tracing and genetic manipulation of stem cells and their associated niche cells. The picture that is emerging is that different stem cell populations utilize diverse processes to ensure maintenance of the stem cell pool accompanied by production of cells committed to regenerate differentiated cells.

Keywords stem cells      Drosophila      mouse      testis      intestine      lineage tracing     
Corresponding Author(s): Gary R. HIME   
Just Accepted Date: 09 January 2015   Online First Date: 28 January 2015    Issue Date: 14 February 2015
 Cite this article:   
Gary R. HIME,Nicole SIDDALL,Katja HORVAY, et al. Analyzing stem cell dynamics: use of cutting edge genetic approaches in model organisms[J]. Front. Biol., 2015, 10(1): 1-10.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-015-1347-1
https://academic.hep.com.cn/fib/EN/Y2015/V10/I1/1
Mouse intestinal epithelial stem cell niche 1. Mammalian system relevant for modeling human intestinal diseases
2. Well characterized Cre drivers are available for genetic manipulation
3. Tissue is accessible to molecules/cells placed in the lumen
4. Tissue can be grown and manipulated in vitro as whole organ culture or as organoids
Drosophila testis stem cell niche 1. A simple, well characterized stem cell niche
2. Numerous cell specific Gal4 drivers are available for genetic manipulation
3. Drosophila genetics allow complex genetic manipulations
4. The rapid life cycle of Drosophila allows multiple alleles to be introduced into an animal
Tab.1  Advantages offered by analysis in the two systems
Fig.1  Gene manipulation in Drosophila male germline stem cells. (A) Schematic representation of the apical tip of the testis. Hub cells (light blue), Cyst progenitor cells (yellow), Germline stem cells (red), Gonialblast (pink), Spermatogonia (dark blue) and Cyst cells (green) are shown. Adapted from Siddall et al. (2006). (B) Wholemount immunohistochemistry in wild type testis demonstrates that GSCs, mitotic spermatogonia and spermatocytes all express Vasa. (C) A mutant testis where the BMP protein, Dpp, has been ectopically expressed in germ cells using NosGal4 x UAS-Dpp. Staining with Vasa demonstrates that spermatogonia fail to differentiate (compared with A). (D) Lineage tracing in a wild type testis via Heatshock-Flp recombinase and an FRT GFP chromosome. A GFP negative stem cell has given rise to cysts of GFP negative spermatogonia and spermatocytes (marked with anti-Vasa, purple). Scale bars are 20 microns.
Fig.2  Lineage tracing in the mouse small intestinal epithelium. (A) Schematic of lineage tracing (blue, lacZ positive cells) from the Lgr5 promoter in a CBC stem cell (arrow) following induction of CreER with tamoxifen over a period of several days. (B) Lineage tracing from Lgr5-EGFP-IRES-CreERT2 and ROSA-loxP-STOP-loxP-lacZ. A ribbon of lacZ positive cells (blue) can been seen in a crypt and extending into a villus. The extent of the crypt in the schematic (A) is indicated by asterisks on the micrograph (B). This experiment was originally demonstrated by Barker et al. (2007).
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