Advances in hematopoietic stem cell research through mouse genetics

Current Opinion in Hematology

Volumn 13, Issue 4, 2006, Pages 209-215

  Miller, Alison ^a   Van Zant, Gary ^a,b  

^a UNIVERSITY OF KENTUCKY MEDICAL CENTER   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Bone marrow transplant; Differentiation; Hematopoietic stem cell; Microarray; Self renewal

Indexed keywords

CALCIUM; CYTOKINE; DNA; STRONTIUM 89;

ANIMAL GENETICS; AUTOCRINE EFFECT; CALCIUM SIGNALING; CELL ADHESION; CELL AGING; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL FATE; CLINICAL RESEARCH; CYTOKINE PRODUCTION; DNA MICROARRAY; ENCHONDRAL OSSIFICATION; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; GENE OVEREXPRESSION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HOMEOBOX; KNOCKOUT MOUSE; LYMPHOCYTE HOMING; LYMPHOCYTE MIGRATION; LYMPHOCYTE SUBPOPULATION; MOUSE; MOUSE STRAIN; MYELOID PROGENITOR CELL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; STEM CELL MOBILIZATION; TRANSCRIPTION REGULATION;

EID: 33747873433     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/01.moh.0000231416.25956.35     Document Type: Review

References (60)

1. Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 2006; 6:93-106.
2. Huang E, Nocka K, Beier DR, et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990; 63:225-233.
3. Copeland NG, Gilbert DJ, Cho BC, et al. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 1990; 63:175-183.
4. Williams DE, Eisenman J, Baird A, et al. Identification of a ligand for the c-kit proto-oncogene. Cell 1990; 63:167-174.
5. Siminovitch L, Till JE, McCulloch EA. Decline in colony-forming ability of marrow cells subjected to serial transplantation into irradiated mice. J Cell Physiol 1964; 64:23-31.
6. Harrison DE, Stone M, Astle CM. Effects of transplantation on the primitive immunohematopoietic stem cell. J Exp Med 1990; 172:431-437.
7. Mauch P, Rosenblatt M, Hellman S. Permanent loss in stem cell self renewal capacity following stress to the marrow. Blood 1988; 72:1193-1196.
8. Hong L, Munugalavadla V, Kapur R. c-Kit-mediated overlapping and unique functional and biochemical outcomes via diverse signaling pathways. Mol Cell Biol 2004; 24:1401-1410.
9. Taichman RS. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 2005; 105:2631-2639.
10. Srour EF, Jetmore A, Wolber FM, et al. Homing, cell cycle kinetics and fate of transplanted hematopoietic stem cells. Leukemia 2001; 15:1681-1684.
11. Nilsson SK, Simmons PJ. Transplantable stem cells: home to specific niches. Curr Opin Hematol 2004; 11:102-106.
12. Moore MA. Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing. J Cell Biochem Suppl 2002; 38:29-38.
13. Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood 2005; 106:1901-1910.
14. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978; 4:7-25.
15. Klassen LW, Birks J, Allen E, Gurney CW. Experimental medullary aplasia. J Lab Clin Med 1972; 80:8-17.
16. Forsberg EC, Prohaska SS, Katzman S, et al. Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet 2005; 1:e28. This work uses microarray analysis of three primitive hematopoietic subpopulations to identify novel potential regulators of hematopoietic stem cell self-renewal and proliferation and adding to the current repertoire of cell surface markers available for cell isolation.
17. Zhong JF, Zhao Y, Sutton S, et al. Gene expression profile of murine long-term reconstituting vs. short-term reconstituting hematopoietic stem cells. Proc Natl Acad Sci U S A 2005; 102:2448-2453.
18. Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005; 121:1109-1121. Through microarray analysis, this study characterizes cell surface receptors specific for hematopoietic stem cells, multipotent progenitors and progenitor cells. They identify the SLAM family of receptors as the first family of receptors whose combinatorial expression predicts primitiveness. These markers were used to view hematopoietic stem cells in tissue section, identifying endothelial niches in both the bone marrow and spleen, supporting other data that there are multiple niches involved in hematopoiesis.
19. Rossi DJ, Bryder D, Zahn JM, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A 2005; 102:9194-9199.
20. Venezia TA, Merchant AA, Ramos CA, et al. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol 2004; 2:e301 [Epub ahead of print].
21. Yilmaz OH, Kiel MJ, Morrison SJ. SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. Blood 2006; 107:924-930. This study builds on a previous study by the same group, utilizing the SLAM code to further investigate its usefulness as a marker for hematopoietic primitiveness and how the expression of these cell surface proteins changes in reconstituted mice, mobilized mice and with age. They determined that the SLAM receptors are robust markers compared with previous markers that may change expression in response to these variables, suggesting a new and more effective protocol for hematopoietic stem cell isolation.
22. Adams GB, Chabner KT, Alley IR, et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 2006; 439:599-603. These researchers directly investigate the interaction between hematopoietic stem cells and local calcium gradients in the endosteal niche. These data show evidence that this niche is specialized by the high local gradient of calcium ion, which binds the calcium receptor and allows interaction between the niche and the homing stem cells, and adds direct evidence in support of the importance of the endosteal niche to hematopoietic stem cell populations.
23. Ema H, Sudo K, Seita J, et al. Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice. Dev Cell 2005; 8:907-914. This work demonstrates that decreases in functional Lnk protein can cause cells to engraft normally but enter cell cycle more frequently, causing an overall increase in hematopoietic stem cell repopulation ability. This work suggests that Lnk could be used as a tool to manipulate hematopoietic stem cell number.
24. Takaki S, Morita H, Tezuka Y, Takatsu K. Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein. Lnk J Exp Med 2002; 195:151-160.
25. Takizawa H, Kubo-Akashi C, Nobuhisa I, et al. Enhanced engraftment of hematopoietic stem/progenitor cells by the transient inhibition of an adaptor protein. Blood 2005; 107:2968-2975. These researchers used short-term transient expression of a dominant negative form of Lnk by plasmid transfection to block Lnk multimerization. This work demonstrates that the effect of decreasing functional Lnk is to increase reconstitution in myeloablated and nonmyeloablated hosts without integration of the plasmid DNA into the cellular genome. This previously unrecognized pathway is an important aspect of hematopoietic stem cell transplantation that will be of further interest for the future.
26. Rodrigues NP, Janzen V, Forkert R, et al. Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis. Blood 2005; 106:477-484. This research shows that GATA-2 not only has a critical role in hematopoietic stem cell development, but also in the maintenance of normal adult stem cell homeostasis by regulation of primitive cell quiescence.
27. Ezoe S, Matsumura I, Nakata S, et al. GATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21(WAF1) and p27(Kip1) proteins. Blood 2002; 100:3512-3520.
28. Heyworth C, Gale K, Dexter M, et al. A GATA-2/estrogen receptor chimera functions as a ligand-dependent negative regulator of self-renewal. Genes Dev 1999; 13:1847-1860.
29. Persons DA, Allay JA, Allay ER, et al. Enforced expression of the GATA-2 transcription factor blocks normal hematopoiesis. Blood 1999; 93:488-499.
30. Tsai FY, Orkin SH. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 1997; 89:3636-3643.
31. -/- on both C57BL/6 and HW80 backgrounds. These mice were used to determine that defects in Stat5 cause engraftment defects, demonstrating the importance of the Stat5 pathway in hematopoietic stem cell seeding of the bone marrow niche.
32. Snow JW, Abraham N, Ma MC, et al. STAT5 promotes multilineage hematolymphoid development in vivo through effects on early hematopoietic progenitor cells. Blood 2002; 99:95-101.
33. Bunting KD, Bradley HL, Hawley TS, et al. Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5. Blood 2002; 99:479-487.
34. Bradley HL, Hawley TS, Bunting KD. Cell intrinsic defects in cytokine responsiveness of STAT5-deficient hematopoietic stem cells. Blood 2002; 100:3983-3989.
35. Akashi K, He X, Chen J, et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 2003; 101:383-389.
36. Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 1997; 91:661-672.
37. Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 2000; 404:193-197.
38. Opferman JT, Iwasaki H, Ong CC, et al. Obligate role of antiapoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307:1101-1104. These researchers used inducible deletion of Mcl-1 to demonstrate its requirement for hematopoiesis in a tissue-specific manner. This gene was shown to be both critical and specific for its regulation of hematopoiesis by ensuring homeostasis of early hematopoietic progenitors, as its inducible deletion caused ablation of the bone marrow.
39. Glimm H, Oh IH, Eaves CJ. Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0). Blood 2000; 96:4185-4193.
40. Fleming WH, Alpern EJ, Uchida N, et al. Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. J Cell Biol 1993; 122:897-902.
41. Passegue E, Wagers AJ, Giuriato S, et al. Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J Exp Med 2005; 202:1599-1611. These data provide the link between hematopoietic stem cell proliferation and cell fate decisions. Specifically, these data showed that the most primitive populations of stem cells have higher levels of cell cycle inhibitors and lower levels of cyclins. Importantly, these data show that long-term repopulation depends on a quiescent state.
42. Walkley CR, Fero ML, Chien WM, et al. Negative cell-cycle regulators cooperatively control self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol 2005; 7:172-178.
43. Yuan Y, Shen H, Franklin DS, et al. In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C. Nat Cell Biol 2004; 6:436-442.
44. Yu H, Yuan Y, Shen H, Cheng T. Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners. Blood 2006; 107:1200-1206.
45. Lawrence HJ, Sauvageau G, Humphries RK, Largman C. The role of HOX homeobox genes in normal and leukemic hematopoiesis. Stem Cells 1996; 14:281-291.
46. Abramovich C, Humphries RK. Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol 2005; 12:210-216.
47. Zhu J, Zhang Y, Joe GJ, et al. NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal. Proc Natl Acad Sci U S A 2005; 102:11728-11733. This study ties together several signaling cascades to show that NF-Ya induces several HOX genes to cause expansion of the primitive hematopoietic stem cell pool. Alterations in these pathways could be developed into therapeutic strategies to increase stem cell number in culture.
48. Lawrence HJ, Christensen J, Fong S, et al. Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells. Blood 2005; 106:3988-3994. These researchers found that loss of HOXA9 causes a severe impairment in hematopoietic stem cell proliferative response that was compensated for by retroviral introduction of HOXA9, demonstrating that HOXA9 could be a major determinant of stem cell growth and self-renewal. This fact could be utilized to increase these parameters in transplant context.
49. Krosl J, Austin P, Beslu N, et al. In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nat Med 2003; 9:1428-1432.
50. Amsellem S, Pflumio F, Bardinet D, et al. Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein. Nat Med 2003; 9:1423-1427.
51. Sauvageau G, Thorsteinsdottir U, Eaves CJ, et al. Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev 1995; 9:1753-1765.
52. Antonchuk J, Sauvageau G, Humphries RK. HOXB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell 2002; 109:39-45.
53. Brun AC, Bjornsson JM, Magnusson M, et al. Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. Blood 2004; 103:4126-4133.
54. Bijl J, Thompson A, Ramirez-Solis R, et al. Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells. Blood 2005; [Epub ahead of print]. These data demonstrate that hematopoietic stem cells can lack up to approximately 30% of active HOX genes and remain fully competent, most likely due to interaction and compensation within the HOX families. Gene expression experiments in this paper detail interactions between the HOXA, HOXB and HOXC clusters.
55. Horan GS, Ramirez-Solis R, Featherstone MS, et al. Compound mutants for the paralogous hoxa-4, hoxb-4 and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed. Genes Dev 1995; 9:1667-1677.
56. Chen F, Capecchi MR. Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions. Dev Biol 1997; 181:186-196.
57. Rancourt DE, Tsuzuki T, Capecchi MR. Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Genes Dev 1995; 9:108-122.
58. Liang Y, Van Zant G. Genetic control of stem-cell properties and stem cells in aging. Curr Opin Hematol 2003; 10:195-202.
59. Geiger H, Rennebeck G, Van Zant G. Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element. Proc Natl Acad Sci U S A 2005; 102:5102-5107. This study describes a quantitative trait locus on chromosome 2 that is specific to the regulation of hematopoietic stem cell frequency in old but not young animals. Additionally, mice congenic for this genetic region were shown to be sensitive to low doses of irradiation, demonstrating that aging in this mouse model is, at least in part, related to DNA repair pathways. Additionally, irradiation in these congenic mice provides a new model for accelerated aging studies.
60. Geiger H, True JM, de Haan G, Van Zant G. Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy. Blood 2001; 98:2966-2972.