Delta-1 Enhances Marrow and Thymus Repopulating Ability of Human CD34(+)CD38(-) Cord Blood Cells

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2002 Oct 24

PMID 12393852

Citations 71

Authors

Kohshi Ohishi

Barbara Varnum-Finney

Irwin D Bernstein

Affiliations

Soon will be listed here.

Abstract

We investigated the effect of Notch signaling, a known regulator of cell fate in numerous developmental systems, on human hematopoietic precursors. We show that activation of endogenous Notch signaling in human CD34(+)CD38(-) cord blood precursors with immobilized Delta-1 in serum-free cultures containing fibronectin and hematopoietic growth factors inhibited myeloid differentiation and induced a 100-fold increase in the number of CD34(+) cells compared with control cultures. Immobilized Delta-1 also induced a multifold expansion of cells with the phenotype of common lymphoid precursors (CD34(+)CD7(+)CD45RA(+)) and promoted the development of cytoplasmic CD3(+) T/NK cell precursors. IL-7 enhanced the promotion of T/NK cell differentiation by immobilized Delta-1, but granulocytic differentiation occurred when G-CSF was added. Transplantation into immunodeficient mice showed a substantial increase in myeloid and B cell engraftment in the marrow and also revealed thymic repopulation by CD3(+) T cells due to cells being cultured for a longer period with immobilized Delta-1. These data suggest that Delta-1 can enhance myeloid and lymphoid marrow-repopulating ability and promote the generation of thymus-repopulating T cell precursors.

Citing Articles

Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate.

Thambyrajah R, Maqueda M, Neo W, Imbach K, Guillen Y, Grases D Nat Commun. 2024; 15(1):1604.

PMID: 38383534 PMC: 10882055. DOI: 10.1038/s41467-024-45716-y.

Ex vivo expansion of human hematopoietic stem cells and clinical applications.

Sakurai M, Ishitsuka K, Becker H, Yamazaki S Cancer Sci. 2024; 115(3):698-705.

PMID: 38221718 PMC: 10921004. DOI: 10.1111/cas.16066.

Progress on methods of T lymphocyte development .

Li Y, Chen X Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023; 51(4):491-499.

PMID: 37202105 PMC: 10265001. DOI: 10.3724/zdxbyxb-2021-0369.

In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation.

Bozhilov Y, Hsu I, Brown E, Wilkinson A Cells. 2023; 12(6).

PMID: 36980237 PMC: 10046976. DOI: 10.3390/cells12060896.

Development and clinical advancement of small molecules for expansion of hematopoietic stem cell.

Li J, Wang X, Ding J, Zhu Y, Min W, Kuang W Acta Pharm Sin B. 2022; 12(6):2808-2831.

PMID: 35755294 PMC: 9214065. DOI: 10.1016/j.apsb.2021.12.006.

References

Ramsfjell V, Bryder D, Bjorgvinsdottir H, Kornfalt S, Nilsson L, Borge O . Distinct requirements for optimal growth and In vitro expansion of human CD34(+)CD38(-) bone marrow long-term culture-initiating cells (LTC-IC), extended LTC-IC, and murine in vivo long-term reconstituting stem cells. Blood. 1999; 94(12):4093-102. View

Pui J, Allman D, Xu L, DeRocco S, Karnell F, Bakkour S . Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity. 1999; 11(3):299-308. DOI: 10.1016/s1074-7613(00)80105-3. View

Ohishi K, Varnum-Finney B, Flowers D, Anasetti C, Myerson D, Bernstein I . Monocytes express high amounts of Notch and undergo cytokine specific apoptosis following interaction with the Notch ligand, Delta-1. Blood. 2000; 95(9):2847-54. View

Tsai S, Fero J, Bartelmez S . Mouse Jagged2 is differentially expressed in hematopoietic progenitors and endothelial cells and promotes the survival and proliferation of hematopoietic progenitors by direct cell-to-cell contact. Blood. 2000; 96(3):950-7. View

Bertrand F, Eckfeldt C, Fink J, Lysholm A, Pribyl J, Shah N . Microenvironmental influences on human B-cell development. Immunol Rev. 2000; 175:175-86. View

Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S . Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med. 2000; 6(11):1278-81. DOI: 10.1038/81390. View

Karanu F, Murdoch B, Gallacher L, Wu D, Koremoto M, Sakano S . The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med. 2000; 192(9):1365-72. PMC: 2193352. DOI: 10.1084/jem.192.9.1365. View

Varnum-Finney B, Wu L, Yu M, Brashem-Stein C, Staats S, Flowers D . Immobilization of Notch ligand, Delta-1, is required for induction of notch signaling. J Cell Sci. 2000; 113 Pt 23:4313-8. DOI: 10.1242/jcs.113.23.4313. View

Canque B, Camus S, Dalloul A, Kahn E, Yagello M, Dezutter-Dambuyant C . Characterization of dendritic cell differentiation pathways from cord blood CD34(+)CD7(+)CD45RA(+) hematopoietic progenitor cells. Blood. 2000; 96(12):3748-56. View

10.

Glimm H, Eisterer W, Lee K, Cashman J, Holyoake T, Nicolini F . Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest. 2001; 107(2):199-206. PMC: 199177. DOI: 10.1172/JCI11519. View

11.

Karanu F, Murdoch B, Miyabayashi T, Ohno M, Koremoto M, Gallacher L . Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells. Blood. 2001; 97(7):1960-7. DOI: 10.1182/blood.v97.7.1960. View

12.

Laughlin M, Barker J, Bambach B, Koc O, Rizzieri D, Wagner J . Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001; 344(24):1815-22. DOI: 10.1056/NEJM200106143442402. View

13.

Gluckman E . Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl J Med. 2001; 344(24):1860-1. DOI: 10.1056/NEJM200106143442410. View

14.

Hao Q, Zhu J, Price M, Payne K, Barsky L, Crooks G . Identification of a novel, human multilymphoid progenitor in cord blood. Blood. 2001; 97(12):3683-90. DOI: 10.1182/blood.v97.12.3683. View

15.

Allman D, Karnell F, Punt J, Bakkour S, Xu L, Myung P . Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells. J Exp Med. 2001; 194(1):99-106. PMC: 2193437. DOI: 10.1084/jem.194.1.99. View

16.

Rossmanith T, Schroder B, Bug G, Muller P, Klenner T, Knaus R . Interleukin 3 improves the ex vivo expansion of primitive human cord blood progenitor cells and maintains the engraftment potential of scid repopulating cells. Stem Cells. 2001; 19(4):313-20. DOI: 10.1634/stemcells.19-4-313. View

17.

Ohishi K, Varnum-Finney B, Serda R, Anasetti C, Bernstein I . The Notch ligand, Delta-1, inhibits the differentiation of monocytes into macrophages but permits their differentiation into dendritic cells. Blood. 2001; 98(5):1402-7. DOI: 10.1182/blood.v98.5.1402. View

18.

Jaleco A, Neves H, Hooijberg E, Gameiro P, Clode N, Haury M . Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med. 2001; 194(7):991-1002. PMC: 2193482. DOI: 10.1084/jem.194.7.991. View

19.

Wilson A, MacDonald H, Radtke F . Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J Exp Med. 2001; 194(7):1003-12. PMC: 2193487. DOI: 10.1084/jem.194.7.1003. View

20.

Stier S, Cheng T, Dombkowski D, Carlesso N, Scadden D . Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood. 2002; 99(7):2369-78. DOI: 10.1182/blood.v99.7.2369. View