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提醒： 因为讲座的部分数据是unpublished data, 所以还希望大家不要下载这个主题下所有的图片，谢谢合作。
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sean morrison 简介：) S$ s% G5 N" P- Y h9 e5 A$ l0 Z; K3 b
http://www.lsi.umich.edu/facultyresearch/labs/morrison/pi0 i7 d! K4 j7 K
" M! z0 g/ a# v5 D" G1 t |Sean Morrison & T, m- z0 F3 c- F+ v" E
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Howard Hughes Medical Institute Biography
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Stem Cell Research at the U of M 6 X9 B; ^; v! P
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' g1 P& ]( m% x4 LSean Morrison is investigating the mechanisms that regulate stem cell function in the nervous and hematopoietic systems, particularly the mechanisms that regulate stem cell self-renewal and stem cell aging, as well as the relationship between stem cell self-renewal and cancer cell proliferation. Parallel studies of these mechanisms in stem cells from two different tissues will reveal the extent to which different types of stem cells employ similar or different mechanisms to regulate these critical functions. In addition to stem cell research, Dr. Morrison has been active in public policy issues surrounding stem cells as Director of the UM Center for Stem Cell Biology, an officer of the International Society for Stem Cell Research, and as a member of the American Society for Cell Biology Public Policy Committee. Michigan recently passed Proposal 2, making Michigan one of three states in the country to protect stem cell research in the state constitution. Morrison, 40, was born in Halifax, Nova Scotia, and completed his undergraduate work at Dalhousie University, where he interrupted his undergraduate studies to perform research after founding an agricultural biotechnology company that developed a biological fertilizer. In 1991 he moved to Stanford University to pursue a Ph.D. As a graduate student in Irving Weissman’s lab Morrison isolated and characterized blood-forming stem cells. As a post-doctoral fellow in the lab of David Anderson at the California Institute of Technology, Morrison developed techniques for the isolation of nervous system stem cells from uncultured tissues. In 1999, Morrison was recruited to join the U-M Medical School faculty as a Biological Sciences Scholar. The Morrison laboratory has published a number of discoveries related to the mechanisms that regulate the maintenance of stem cells throughout life, and how these mechanisms change during aging. For example, the Morrison laboratory’s work suggests that aging tissues exhibit reduced regenerative capacity partly because stem cells induce tumor suppressor mechanisms as they age, reducing stem cell frequency and function. Dr. Morrison was a Searle Scholar from 2000-2003, was named to Technology Review Magazine's list of 100 young innovators for 2002, received Wired Magazine's Rave Award for Science in 2003, and was given the Presidential Early Career Award for Scientists and Engineers by George W. Bush in 2003. More recently Dr. Morrison was awarded the McCulloch and Till Award by the International Society for Hematology and Stem Cells (2007), and the Harland Winfield Mossman Award by the American Association of Anatomists (2008). Dr. Morrison is a Howard Hughes Medical Institute investigator and has received funding from the National Institutes of Health, the Department of Defense, and various private foundations.: X; I m; p; d& r
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研究方向 Research2 t7 H7 U" Q1 D1 @, C% c; Q+ m
The Regulation of Stem Cell Self-Renewal | Stem Cell Aging | Stem Cell Self-Renewal Versus Cancer Cell Proliferation
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; i" @9 ~: r( }To Visit The University of Michigan Stem Cell Research Website, click here
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" b" h, u8 K) c9 {* W7 Y5 R1 U9 YWe are investigating the mechanisms that regulate stem cell function in the nervous and hematopoietic systems. Hematopoietic stem cells, which give rise to all blood and immune system cells, and neural stem cells, which give rise to the central and peripheral nervous systems, are among the best-characterized stem cells. Many fundamental questions remain, however, regarding the mechanisms that regulate their functions. Our goal is to integrate what we know about stem cells in different tissues to understand the extent to which they employ similar or different mechanisms to regulate critical functions. We have focused on the mechanisms that regulate stem cell self-renewal and stem cell aging because these processes encompass fundamental questions in cell and developmental biology. Since cancer cells hijack these self-renewal mechanisms, we also evaluate the role these mechanisms play in cancer.
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The Regulation of Stem Cell Self-Renewal2 q; U* B- K' s3 A) w
The maintenance of many adult tissues depends upon the persistence of stem cells throughout life. Stem cells are maintained in adult tissues by self-renewal—the process by which stem cells divide to make more stem cells. By better understanding this process we gain insights into how tissues develop and regenerate, how reduced self-renewal can lead to degenerative disease, and how increased self-renewal can lead to tumorigenesis. We have discovered that networks of proto-oncogenes and tumor suppressors that control cancer cell proliferation also regulate stem cell self-renewal, but that these networks do not generically regulate the proliferation of all cells. Restricted progenitor proliferation does not require many of the mechanisms that regulate stem cell self-renewal.: }& _. c0 s8 V1 z
( i5 D, k6 k. tProto-oncogenes tend to promote tissue regeneration by promoting stem cell function but must be balanced with tumor-suppressor activity to avoid neoplastic proliferation. Gate keeping tumor suppressors tend to inhibit regeneration by negatively regulating cell division, but also prevent cancer. Care-taking tumor suppressors tend to promote stem cell maintenance and tissue regeneration by protecting cellular and genomic integrity.5 \3 j1 M/ i. J% F- g
* \# V8 p7 t# `1 mWe take forward and reverse genetic approaches to identify new genes that regulate stem cell self-renewal. Each time we identify a self-renewal regulator we learn something new about how self-renewal occurs by examining the downstream mechanisms by which the gene product functions. For example, we have identified two proto-oncogenic chromatin regulators, Bmi-1 and Hmga2, that promote stem cell self-renewal by negatively regulating the expression of the Ink4a and Arf tumor suppressors. These studies demonstrated that the networks of proto-oncogenes and tumor suppressors that regulate stem cell self-renewal change throughout life in response to changing tissue demands and the changing risk of cancer. Imbalances within these networks cause cancer or premature declines in stem cell activity that resemble degenerative disease or premature aging.! n4 a. V- W: l2 _" m7 U0 a) T1 O
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Stem Cell Aging
0 ?2 c( a) L2 L" jUntil recently there has been little insight into why aging tissues exhibit reduced regenerative capacity. Aging is also associated with increased cancer incidence in tissues that contain stem cells. These observations suggest a link between aging and stem cell function because stem cells drive the regeneration of most tissues, and because many cancers arise from the transformation of stem cells (or at least require hyper-activation of stem cell self-renewal pathways). Much of age-related morbidity in mammals may be determined by the influence of aging on stem cell function. We have found that stem cells from the hematopoietic and nervous systems undergo strikingly conserved changes in their properties as they age, including declining self-renewal capacity.1 O/ E5 ?. \6 c
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( x: Y8 Q& f1 q$ L3 r0 xWe discovered that the networks of proto-oncogenes and tumor suppressors that regulate stem cell self-renewal and cancer cell proliferation (see above) also regulate stem cell aging. For example, Hmga2 expression declines and Ink4a expression increases with age, reducing stem cell frequency and function. By deleting Ink4a from mice, we partially rescued the decline in stem cell function with age and enhanced the regenerative capacity of aging tissues. Indeed, we have identified an entire pathway of genes upstream of Ink4a that regulates changes in stem cell function during aging. In this way, networks of proto-oncogenes and tumor suppressors change throughout life to balance tissue regeneration with tumor suppression: proto-oncogenic signals dominate during fetal development when tissue growth is rapid but cancer risk is low and tumor suppressor mechanisms are amplified during aging when there is little tissue growth but cancer risk is high. We use forward and reverse genetics to identify the molecular mechanisms that allow these networks to strike this dynamic balance.
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- ]9 P8 @" L, C8 a4 q! s' KStem Cell Self-Renewal Versus Cancer Cell Proliferation! N8 l; ^, ?8 a* i8 |/ a/ Q
Cancer cells often hijack stem cell self-renewal mechanisms by acquiring mutations that over-activate these pathways. Even when this occurs, we have discovered it is possible to identify mechanistic differences between normal stem cell self-renewal and cancer cell proliferation. For example, deletion of the Pten tumor suppressor has different effects on the self-renewal of normal hematopoietic stem cells and the proliferation of leukemia cells. Conditional deletion of Pten in adult hematopoietic cells rapidly leads to leukemogenesis. In contrast, Pten deletion cell autonomously leads to the depletion of hematopoietic stem cells. These effects of Pten deficiency can be inhibited by the drug rapamycin, which inhibits mTor, a kinase that is activated after Pten deletion. Our studies suggest that the degree of mTor activation is a key determinant of stem cell maintenance. Rapamycin treatment of Pten-deficient mice not only eliminates leukemia cells but also restores normal hematopoietic stem cell function. Mechanistic differences between normal stem cells and cancer cells can thus be targeted to eliminate cancer cells without damaging normal stem cells. Identification of additional such drugs will reduce the toxicity of chemotherapy and facilitate normal tissue regeneration after cancer treatment.: {! G& `+ t+ N K6 X# e, h; H
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Not all cancer cells have the same capacity to proliferate. In some cancers most cancer cells appear to have a limited ability to proliferate, while in the same tumors, minority populations of "cancer stem cells" retain the capacity to proliferate indefinitely. Data from our lab and others indicate that acute and chronic myeloid leukemia appear to follow a cancer stem cell model. In both cases, leukemogenic cells are rare, phenotypically distinct from the vast majority of other leukemia cells, and robustly hierarchically organized. However, it is not clear how generalizable the cancer stem cell model is. In other human and mouse cancers we have studied, including melanoma, tumorigenic capacity is a common attribute of many cancer cells and we have been unable to find any clear evidence of hierarchical organization. Our impression is that the growth and progression of many cancers are driven by many cells rather than by cancer stem cells. It will be critical to determine which cancers follow the stem cell model and which do not to devise appropriate therapeutic strategies.
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Publications
' S( |. v- J6 K* @3 I/ y' H0 E( \0 NRecent Articles | Articles (1994-2004) | Review Articles | Editorial Material | Letters6 G8 w9 }/ c, I
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* p" I- n2 ?& A; W' O6 l* [Song J., Kiel M.J., Wang Z., Wang J., Taichman R.S., S.J. Morrison, Krebsbach P.H. 2010. An in vivo model to study and manipulate the hematopoietic stem cell niche. Blood. PubMed Links+ X0 }8 ^6 Q% Y% s& B
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Mosher J.T., Pemberton T.J., Harter K., Wang C., Buzbas E.O., Dvorak P., Simon C., S.J. Morrison, Rosenberg N.A. 2010. Lack of population diversity in commonly used human embryonic stem-cell lines. New England Journal of Medicine 362(2):183-5. PubMed Links
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Shackleton M., Quintana E., Fearon E.R., S.J. Morrison. 2009. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 138(5):822-9. PubMed Links
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Oravecz-Wilson K.I., Philips S.T., Yilmaz O.H., Ames H.M., Li L., Crawford B.D., Gauvin A.M., Lucas P.C., Sitwala K., Downing J.R., S.J. Morrison, Ross T.S. 2009. Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder. Cancer Cell 16(2):137-48. PubMed Links
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/ C' p3 \1 O4 V O, C4 K6 } A1 WHe S., Iwashita T., Buchstaller J., Molofsky A.V., Thomas D., S.J. Morrison. 2009. Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo. Developmental Biology 328(2): 257-72.PubMed Link
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Levi B.P., O.H. Yilmaz, G. Duester, and S.J. Morrison. 2009. Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. Blood 113:1670-80.PubMed Link$ o, L# E/ K4 a: ^0 o9 ^% }
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Kiel M.J., M. Acar, G.L. Radice and S.J.Morrison. 2009. Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance. Cell Stem Cell 4:170-9.PubMed Link4 ^3 j" c. h9 e/ Z. Q6 v7 n
! x F/ M. v3 w& b) _" N$ G) wQuintana, E., M. Shackleton, M. Sabel, D.Fullen, T.M. Johnson, and S.J. Morrison. 2008. Efficient tumor formation by single human melanoma cells. Nature 456:593-598.PubMed Link
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Nishino, J., I. Kim, K. Chada, and S.J. Morrison. 2008. Hmga2 promotes neural stem cell self-renewal in young, but not old, mice by reducing p16 Ink4a and p19Arf expression. Cell 135:227-239.PubMed Link
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& ]& W y3 `% hKiel M.J., O.H. Yilmaz and S.J. Morrison. 2008. CD150- cells are transiently reconstituting multipotent progenitors with little or no stem cell activity. Blood 111:4413-4. PubMed Link
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0 J7 @' @3 x1 E6 PKiel, M.J. and S.J. Morrison. 2008. Uncertainty in the niches that maintain haematopoietic stem cells. Nature Reviews Immunology 8:290-301.PubMed Link( a5 g' W1 {9 H. b
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Morrison, S.J. and A. Spradling. 2008. Stem Cells and Niches: Mechanisms that promote stem cell maintenance throughout life. Cell 132:598-611.PubMed Link; Y" P9 w! n0 _
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Joseph, N.M., J.T. Mosher, J. Buchstaller, P. Snider, P.E. McKeever, M. Lim, S. J. Conway, L.F. Parada, Y. Zhu, and S. J. Morrison. 2008. The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 13: 129-140.PubMed Link# }. h' h" e1 l! [6 X3 ]
: s* S! K: p8 qZhang, Y., S. N. Zolov, C.Y. Chow, S.G. Slutsky, S.C. Richardson, R.C. Piper, B. Yang, J.J. Nau, R.J. Westrick, S.J. Morrison, M.H. Meisler, and L.S. Weisman. 2007. Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice. Proceedings of the National Academy of Sciences USA 104:17518-17523. PubMed Link$ ?5 z1 Q# C) f0 J. u
# s* }* d/ G9 ^# R9 r6 aKiel M.J., S. He, R. Ashkenazi, S.N. Gentry, M. Teta, J.A. Kushner, T. L. Jackson and S.J. Morrison. 2007. Hematopoietic stem cells do not asymmetrically segregate chromosomes or retain bromodeoxyuridine. Nature 449:238-42. PubMed Link
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. ?4 b" u3 X0 H5 Z6 zKiel M.J., G.L. Radice and S.J. Morrison. 2007. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cells 1:204-217. Cell Stem Cells Summary
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! g. S- u( B G2 \# ~Kim, I., T.L. Saunders and S.J. Morrison. 2007. Sox17 dependence distinguishes the transcriptional regulation of fetal from adult hematopoietic stem cells. Cell 130:470-483. PubMed Link6 O3 B @2 |2 E+ q4 {/ f. {5 h D0 Q
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Kim, I., He, S. H., Yilmaz, O. H., Kiel, M. J., & Morrison, S. J. (2006). Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors. Blood 108:737-744. PubMed Link: a1 W6 H: V) a3 D3 m% L
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Molofsky, A.V., Slutsky, S.G., Joseph, N.M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N., & Morrison, S.J. (2006). Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448-452 PubMed Link$ r3 A2 u6 r. H/ Z! d
0 t; V# U: y0 hYilmaz, O. H., Kiel, M. J., & Morrison, S. J. (2006). SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. Blood 107:924-930. PubMed Link
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8 [* ^2 ]2 w6 r& ?6 aYilmaz, O. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006). Pten dependence distinguishes hematopoietic stem cells from leukemia-initiating cells. Nature 441:475-482. PubMed Link
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Morrison, S. J., & Kimble, J. (2006). Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441:1068-1074. Nature 441:1068-1074. PubMed Link
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Molofsky, A. V., He, S. H., Bydon, M., Morrison, S. J., & Pardal, R. (2005). Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16(Ink4a) and P19(Arf) senescence pathways. Genes & Development 19:1432-1437. PubMed Link
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Kim, I., Yilmaz, O. H., & Morrison, S. J. (2005). CD144 (VE-cadherin) is transiently expressed by fetal liver hematopoietic stem cells. Blood 106:903-905. PubMed Link
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Joseph, N. M., & Morrison, S. J. (2005). Toward an understanding of the physiological function of mammalian stem cells. Developmental Cell 9:173-183. PubMed Link! r, z1 Q$ g" a+ D
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Kiel, M. J., Yilmaz, O. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005). SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121:1109-1121. PubMed Link$ G# r6 P" t4 `$ Q' Z
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Kiel, M. J., Iwashita, T., Yilmaz, O. H., & Morrison, S. J. (2005). Spatial differences in hematopoiesis but not in stem cells indicate a lack of regional patterning in definitive hematopoietic stem cells. Developmental Biology 283:29-39. PubMed
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+ f6 [! S5 S- k+ p ^Articles (1994-2004)
& @( F- y0 f+ m( s( { r6 |" H7 ?Joseph, N. M., Mukouyama, Y. S., Mosher, J. T., Jaegle, M., Crone, S. A., Dormand, E. L., Lee, K. F., Meijer, D., Anderson, D. J., & Morrison, S. J. (2004). Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development 131:5599-612. PubMed Link2 L o2 ]& L6 P% u1 }
2 V2 N) t+ \) D8 d" u; P+ j) S3 D9 wOravecz-Wilson, K. I., Kiel, M. J., Li, L., Rao, D. S., Saint-Dic, D., Kumar, P. D., Provot, M. M., Hankenson, K. D., Reddy, V. N., Lieberman, A. P., Morrison, S. J., & Ross, T. S. (2004). Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects, and cataracts. Human Molecular Genetics 13:851-867. PubMed Link
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4 I5 u0 W: w% U, k$ u i. R* r8 V. \Park, I. K., Morrison, S. J., & Clarke, M. F. (2004). Bmi1, stem cells, and senescence regulation. Journal of Clinical Investigation 113:175-179. PubMed Link
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# [# |, k" k; fMolofsky, A. V., Pardal, R., Iwashita, T., Park, I. K., Clarke, M. F., & Morrison, S. J. (2003). Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962-967. PubMed Link
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0 u6 h9 m" }0 c% ~, eKruger, G. M., Mosher, J. T., Tsai, T. H., Yeager, K. J., Iwashita, T., Gariepy, C. E., & Morrison, S. J. (2003). Temporally distinct requirements for endothelin receptor B in the generation and migration of gut neural crest stem cells. Neuron 40:917-929. PubMed Link
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Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the USA 100:3983-88. [Correction: 100, 6890.] PubMed Link
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- ^& y8 t% a6 C; C& dPark, I. K., Qian, D. L., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003). Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302-5. PubMed Link
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Alvarez-Dolado, M., Pardal, R., Garcia-Vardugo, J. M., Fike, J. R., Lee, H. O., Pfeffer, K., Lois, C., Morrison, S. J., & Alvarez-Buylla, A. (2003). Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968-73. PubMed Link* [' K, d ^$ G/ o7 m3 u
* d7 u( q5 l9 Z+ ~( H4 Y. s4 eIwashita, T., Kruger, G. M., Pardal, R., Kiel, M. J., & Morrison, S. J. (2003). Hirschsprung disease is linked to defects in neural crest stem cell function. Science 301:972-976. PubMed Link+ D6 F+ z$ v$ A8 b
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Kruger, G. M., & Morrison, S. J. (2002). Brain repair by endogenous progenitors. Cell 110:399-402. PubMed Link' \. _% `% q1 m- n& b G( i
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Kubu, C. J., Orimoto, K., Morrison, S. J., Weinmaster, G., Anderson, D. J., & Verdi, J. M. (2002). Developmental changes in Notch1 and Numb expression mediated by local cell-cell interactions underlie progressively increasing delta sensitivity in neural crest stem cells. Developmental Biology 244:199-214. PubMed Link
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8 i! f% q; |" {0 T8 hMorrison, S. J., Qian, D., Jerabek, L., Thiel, B. A., Park, I. K., Ford, P. S., Kiel, M. J., Schork, N. J., Weissman, I. L., & Clarke, M. F. (2002). A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. Journal of Immunology 168:635-642. PubMed Link1 i" v" d X" i6 m- ~) s$ }% e
% [% |) K% Q9 s& i9 \Bixby, S., Kruger, G. M., Mosher, J. T., Joseph, N. M., & Morrison, S. J. (2002). Cell-intrinsic differences between stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron 35:643-656. PubMed Link
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; f4 V M' p1 C- M4 r! EKruger, G. M., Mosher, J. T., Bixby, S., Joseph, N., Iwashita, T., & Morrison, S. J. (2002). Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 35:657-669. PubMed Link
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Morrison, S. J. (2001). Stem cell potential: Can anything make anything? Current Biology 11:R7-R9. PubMed Link g3 z* | Y; ]8 S
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Morrison, S. J. (2001). Neuronal differentiation: Proneural genes inhibit gliogenesis. Current Biology 11:R349-R351. PubMed Link
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* _; v( p, }4 E7 H7 X; hMorrison, S. J. (2001). Neuronal potential and lineage determination by neural stem cells. Current Opinion in Cell Biology 13:666-672. PubMed Link9 a6 m- u/ B# Z0 Z3 P% }; @: x6 [
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White, P. M., Morrison, S. J., Orimoto, K., Kubu, C. J., Verdi, J. M., & Anderson, D. J. (2001). Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals. Neuron 29:57-71. PubMed Link# c X, C, u+ Y' R
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Morrison, S. J., Perez, S. E., Qiao, Z., Verdi, J. M., Hicks, C., Weinmaster, G., & Anderson, D. J. (2000). Transient notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101:499-510. PubMed Link+ ?; ~/ ]$ k7 w% T) v( G6 }
! B3 I/ A n6 o4 `$ W) t) dMorrison, S. J., Csete, M., Groves, A. K., Melega, W., Wold, B., & Anderson, D. J. (2000). Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. Journal of Neuroscience 20:7370-7376. PubMed Link
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4 m* Y% Q/ q* ]- {" f1 B4 IMorrison, S. J., White, P. M., Zock, C., & Anderson, D. J. (1999). Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 96:737-749. PubMed Link; E+ `/ N7 z# }" I
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Cheshier, S. P., Morrison, S. J., Liao, X. S., & Weissman, I. L. (1999). In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proceedings of the National Academy of Sciences of the USA 96:3120-3125. PubMed Link8 @) ~* Z4 a2 J! g8 d( w! L
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Klug, C. A., Morrison, S. J., Masek, M., Hahm, K., Smale, S. T., & Weissman, I. L. (1998). Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proceedings of the National Academy of Sciences of the USA 95:657-662. PubMed Link& ~/ z1 s4 H8 N
R. |) l) g' j- Z. yMorrison, S. J., Wandycz, A. M., Hemmati, H. D., Wright, D. E., & Weissman, I. L. (1997). Identification of a lineage of multipotent hematopoietic progenitors. Development 124:1929-1939. PubMed Link6 {* {/ Y( O6 \4 Q1 w! U
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Morrison, S. J., Wright, D. E., & Weissman, I. L. (1997). Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization. Proceedings of the National Academy of Sciences of the USA 94:1908-1913. PubMed Link
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Morrison, S. J., Prowse, K. R., Ho, P., & Weissman, I. L. (1996). Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5:207-216. PubMed Link
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/ P& p1 [/ J5 J+ K; m8 Z2 y* a8 fMorrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A., & Weissman, I. L. (1996). The aging of hematopoietic stem cells. Nature Medicine 2:1011-1016. PubMed Link* Q+ b% Q/ N V2 k! f
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Morrison, S. J., & Weissman, I. L. (1995). Heterogeneity of hematopoietic stem cells - Implications for clinical applications. Proceedings of the Association of American Physicians 107:187-194. PubMed Link
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Morrison, S. J., Hemmati, H. D., Wandycz, A. M., & Weissman, I. L. (1995). The purification and characterization of fetal liver hematopoietic stem cells. Proceedings of the National Academy of Sciences of the USA 92:10302-10306. PubMed Link
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' _0 w& y: G" P' M, m( QMorrison, S. J., & Weissman, I. L. (1994). The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1:661-673. PubMed Link |
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发表于 2010-4-12 18:16
