Molecular analysis of stem cells and their descendants during cell turnover and regeneration in the planarian Schmidtea mediterranea.
In adult planarians, the replacement of cells lost to physiological turnover or injury is sustained by the proliferation and differentiation of stem cells known as neoblasts. Neoblast lineage relationships and the molecular changes that take place during differentiation into the appropriate cell types are poorly understood. Here we report the identification and characterization of a cohort of genes specifically expressed in neoblasts and their descendants. We find that genes with severely downregulated expression after irradiation molecularly define at least three discrete subpopulations of cells. Simultaneous BrdU labeling and in situ hybridization experiments in intact and regenerating animals indicate that these cell subpopulations are related by lineage. Our data demonstrate not only the ability to measure and study the in vivo population dynamics of adult stem cells during tissue homeostasis and regeneration, but also the utility of studies in planarians to broadly inform stem cell biology in adult organisms.
Eisenhoffer
George T
GT
Department of Neurobiology and Anatomy, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Kang
Hara
H
Sánchez Alvarado
Alejandro
A
D000818:Animals; D002454:Cell Differentiation; D015536:Down-Regulation / Q000528:radiation effects; D020869:Gene Expression Profiling; D010932:Planarians / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*
Science. 2005 Nov 25;310(5752):1327-30
16311336
Cell. 2000 Jan 7;100(1):157-68
10647940
Dev Growth Differ. 2007 Sep;49(7):571-81
17587325
Dev Cell. 2005 Feb;8(2):193-202
15691761
Annu Rev Cell Dev Biol. 2004;20:725-57
15473858
Cell. 2007 Feb 9;128(3):445-58
17289566
Science. 2002 Sep 27;297(5590):2256-9
12215650
J Biol Chem. 2002 Apr 19;277(16):14005-10
11830591
Cell. 2004 Sep 3;118(5):635-48
15339667
Genome Biol. 2007;8(4):R62
17445279
C R Hebd Seances Acad Sci. 1947 May 12;224(19):1387
20256096
Genesis. 2002 Apr;32(4):293-8
11948917
Nat Med. 2001 Apr;7(4):393-5
11283651
Prog Neurobiol. 2004 Oct;74(2):77-99
15518954
Dev Biol. 2005 Sep 1;285(1):101-15
16040025
Neuromuscul Disord. 2007 Aug;17(8):639-50
17588756
J Submicrosc Cytol Pathol. 1997 Jan;29(1):91-7
9066147
Development. 2007 Sep;134(17):3121-31
17670787
Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11861-5
12917490
Nat Med. 1996 Sep;2(9):1011-6
8782459
Science. 2001 Aug 10;293(5532):1074-80
11498575
Oncogene. 1999 Jun 10;18(23):3501-10
10376528
Int J Dev Biol. 1991 Jun;35(2):101-8
1722693
Development. 2002 Dec;129(24):5659-65
12421706
Annu Rev Genet. 2007;41:83-105
18076325
Dev Cell. 2006 Aug;11(2):159-69
16890156
Curr Biol. 2001 Jan 9;11(1):R7-9
11166187
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18491-6
16344473
Immunity. 2007 Apr;26(4):407-19
17433729
BMC Dev Biol. 2005 May 26;5:9
15918910
Dev Biol. 2000 Apr 15;220(2):142-53
10753506
Biol Reprod. 1998 Jun;58(6):1437-44
9623603
Nat Cell Biol. 2008 Jun;10(6):731-9
18454139
Mol Cell Biol. 1991 Mar;11(3):1372-81
1996099
Am J Pathol. 2004 May;164(5):1773-82
15111323
Science. 2000 Oct 13;290(5490):328-30
11030649
J Biol Chem. 2007 Dec 28;282(52):37894-905
17971452
J Biol Chem. 2004 Jul 16;279(29):30850-5
15136563
Nat Med. 2005 Dec;11(12):1351-4
16288281
Genes Dev. 2006 Nov 1;20(21):3010-21
17079688
Science. 2005 Dec 2;310(5753):1487-9
16322456
Nature. 2004 Dec 23;432(7020):1036-40
15616564
Cell. 2001 Aug 24;106(4):511-21
11525736
Nature. 2006 Jan 26;439(7075):470-4
16340960
Dev Growth Differ. 2006 Aug;48(6):371-80
16872450
Dev Biol. 2002 Nov 1;251(1):59-73
12413898
Genes Dev. 2005 Jun 15;19(12):1432-7
15964994
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499
J Biol Chem. 1985 Aug 5;260(16):9114-6
3894352
Development. 1997 May;124(10):1929-39
9169840
Dev Cell. 2005 May;8(5):635-49
15866156
Oncogene. 2004 Feb 26;23(8):1539-48
14661056