Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

Xiaona Zheng^a,
Guangyu Zhang^a,
Yandong Gong^a,
Xiaowei Ning^a,
Zhijie Bai^a,
Jian He^a,
Fan Zhou^{b, c},
Yanli Ni^d,
Yu Lan^{e
, ,},
Bing Liu^{a, d, e, f
, ,}

a.
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China
b.
Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, School of Life Sciences, Peking University, Beijing, China
c.
Biomedical Pioneering Innovation Center and Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China
d.
State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China
e.
Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL); Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, China
f.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, 300020, China

More Information

Corresponding author: E-mail address: rainyblue_1999@126.com (Yu Lan); E-mail address: bingliu17@yahoo.com (Bing Liu)

摘要

- /
- /
- /
Abstract: The functional heterogeneity of hematopoietic stem cells (HSCs) has been comprehensively investigated by single-cell transplantation assay. However, the heterogeneity regarding their physiological contribution remains an open question, especially for those with life-long hematopoietic fate of rigorous self-renewing and balanced differentiation capacities. In this study, we revealed that Procr expression was detected principally in phenotypical vascular endothelium co-expressing Dll4 and CD44 in the mid-gestation mouse embryos, and could enrich all the HSCs of the embryonic day 11.5 (E11.5) aorta-gonad-mesonephros (AGM) region. We then used a temporally restricted genetic tracing strategy to irreversibly label the Procr-expressing cells at E9.5. Interestingly, most labeled mature HSCs in multiple sites (such as AGM) around E11.5 were functionally categorized as lymphomyeloid-balanced HSCs assessed by direct transplantation. Furthermore, the labeled cells contributed to an average of 7.8% of immunophenotypically defined HSCs in E14.5 fetal liver (FL) and 6.9% of leukocytes in peripheral blood (PB) during one-year follow-up. Surprisingly, in aged mice of 24 months, the embryonically tagged cells displayed constant contribution to leukocytes with no bias to myeloid or lymphoid lineages. Altogether, we demonstrated, for the first time, the existence of a subtype of physiologically long-lived balanced HSCs as hypothesized, whose precise embryonic origin and molecular identity await further characterization.
- Genetic lineage tracing /
- Hematopoietic stem cells /
- Heterogeneity /
- Aorta-gonad-mesonephros region

HTML全文

参考文献(36)

[1]	Adolfsson, J., Borge, O.J., Bryder, D., Theilgaard-Monch, K., Astrand-Grundstrom, I., Sitnicka, E., Sasaki, Y., Jacobsen, S.E., 2001. Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 15, 659-669.
[2]	Beaudin, A.E., Boyer, S.W., Perez-Cunningham, J., Hernandez, G.E., Derderian, S.C., Jujjavarapu, C., Aaserude, E., MacKenzie, T., Forsberg, E.C., 2016. A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells. Cell stem cell 19, 768-783.
[3]	Benz, C., Copley, M.R., Kent, D.G., Wohrer, S., Cortes, A., Aghaeepour, N., Ma, E., Mader, H., Rowe, K., Day, C., Treloar, D., Brinkman, R.R., Eaves, C.J., 2012. Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs. Cell stem cell 10, 273-283.
[4]	Bryder, D., Rossi, D.J., Weissman, I.L., 2006. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 169, 338-346.
[5]	Chong, D.C., Koo, Y., Xu, K., Fu, S., Cleaver, O., 2011. Stepwise arteriovenous fate acquisition during mammalian vasculogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 240, 2153-2165.
[6]	Christensen, J.L., Weissman, I.L., 2001. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proceedings of the National Academy of Sciences of the United States of America 98, 14541-14546.
[7]	Christensen, J.L., Wright, D.E., Wagers, A.J., Weissman, I.L., 2004. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2, E75.
[8]	Cumano, A., Dieterlen-Lievre, F., Godin, I., 1996. Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 86, 907-916.
[9]	de Bruijn, M.F., Ma, X., Robin, C., Ottersbach, K., Sanchez, M.J., Dzierzak, E., 2002a. Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta, Immunity, 2002/06/07 ed, pp. 673-683.
[10]	de Bruijn, M.F., Speck, N.A., Peeters, M.C., Dzierzak, E., 2000. Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. The EMBO journal 19, 2465-2474.
[11]	Dykstra, B., Kent, D., Bowie, M., McCaffrey, L., Hamilton, M., Lyons, K., Lee, S.J., Brinkman, R., Eaves, C., 2007. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell stem cell 1, 218-229.
[12]	Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., de Haan, G., 2011. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. The Journal of experimental medicine 208, 2691-2703.
[13]	Ema, H., Nakauchi, H., 2000. Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95, 2284-2288.
[14]	Ema, H., Sudo, K., Seita, J., Matsubara, A., Morita, Y., Osawa, M., Takatsu, K., Takaki, S., Nakauchi, H., 2005. Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice. Developmental cell 8, 907-914.
[15]	Gekas, C., Dieterlen-Lievre, F., Orkin, S.H., Mikkola, H.K., 2005. The placenta is a niche for hematopoietic stem cells. Developmental cell 8, 365-375.
[16]	Gekas, C., Rhodes, K.E., Van Handel, B., Chhabra, A., Ueno, M., Mikkola, H.K., 2010. Hematopoietic stem cell development in the placenta. The International journal of developmental biology 54, 1089-1098.
[17]	Godin, I., Cumano, A., 2002. The hare and the tortoise: an embryonic haematopoietic race. Nature reviews. Immunology 2, 593-604.
[18]	Iwasaki, H., Arai, F., Kubota, Y., Dahl, M., Suda, T., 2010. Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver. Blood 116, 544-553.
[19]	Jaffredo, T., Gautier, R., Eichmann, A., Dieterlen-Lievre, F., 1998. Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development 125, 4575-4583.
[20]	Jaffredo, T., Nottingham, W., Liddiard, K., Bollerot, K., Pouget, C., de Bruijn, M., 2005. From hemangioblast to hematopoietic stem cell: an endothelial connection? Experimental hematology 33, 1029-1040.
[21]	Kent, D.G., Copley, M.R., Benz, C., Wohrer, S., Dykstra, B.J., Ma, E., Cheyne, J., Zhao, Y., Bowie, M.B., Zhao, Y., Gasparetto, M., Delaney, A., Smith, C., Marra, M., Eaves, C.J., 2009. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood 113, 6342-6350.
[22]	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.
[23]	Kumaravelu, P., Hook, L., Morrison, A.M., Ure, J., Zhao, S., Zuyev, S., Ansell, J., Medvinsky, A., 2002. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development 129, 4891-4899.
[24]	Medvinsky, A., Dzierzak, E., 1996. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897-906.
[25]	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 United States of America 92, 10302-10306.
[26]	Morrison, 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.
[27]	Muller, A.M., Medvinsky, A., Strouboulis, J., Grosveld, F., Dzierzak, E., 1994. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1, 291-301.
[28]	North, T.E., de Bruijn, M.F., Stacy, T., Talebian, L., Lind, E., Robin, C., Binder, M., Dzierzak, E., Speck, N.A., 2002. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16, 661-672.
[29]	Taylor, E., Taoudi, S., Medvinsky, A., 2010. Hematopoietic stem cell activity in the aorta-gonad-mesonephros region enhances after mid-day 11 of mouse development. The International journal of developmental biology 54, 1055-1060.
[30]	Wang, D., Cai, C., Dong, X., Yu, Q.C., Zhang, X.O., Yang, L., Zeng, Y.A., 2015. Identification of multipotent mammary stem cells by protein C receptor expression. Nature 517, 81-84.
[31]	Wheatley, S.C., Isacke, C.M., Crossley, P.H., 1993. Restricted expression of the hyaluronan receptor, CD44, during postimplantation mouse embryogenesis suggests key roles in tissue formation and patterning. Development 119, 295-306.
[32]	Yang, L., Bryder, D., Adolfsson, J., Nygren, J., Mansson, R., Sigvardsson, M., Jacobsen, S.E., 2005. Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 105, 2717-2723.
[33]	Ye, H., Wang, X., Li, Z., Zhou, F., Li, X., Ni, Y., Zhang, W., Tang, F., Liu, B., Lan, Y., 2017. Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence. Cell research.
[34]	Yokomizo, T., Dzierzak, E., 2010. Three-dimensional cartography of hematopoietic clusters in the vasculature of whole mouse embryos. Development 137, 3651-3661.
[35]	Zhou, F., Li, X., Wang, W., Zhu, P., Zhou, J., He, W., Ding, M., Xiong, F., Zheng, X., Li, Z., Ni, Y., Mu, X., Wen, L., Cheng, T., Lan, Y., Yuan, W., Tang, F., Liu, B., 2016. Tracing haematopoietic stem cell formation at single-cell resolution. Nature 533, 487-492.
[36]	Zovein, A.C., Hofmann, J.J., Lynch, M., French, W.J., Turlo, K.A., Yang, Y., Becker, M.S., Zanetta, L., Dejana, E., Gasson, J.C., Tallquist, M.D., Iruela-Arispe, M.L., 2008. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell stem cell 3, 625-636.

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 139
HTML全文浏览量: 49
PDF下载量: 2
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

doi: 10.1016/j.jgg.2019.10.005

计量

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

Corresponding author: E-mail address: rainyblue_1999@126.com (Yu Lan); E-mail address: bingliu17@yahoo.com (Bing Liu)

计量

目录

留言板

doi: 10.1016/j.jgg.2019.10.005

计量

出版历程

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

Corresponding author: E-mail address: rainyblue_1999@126.com (Yu Lan); E-mail address: bingliu17@yahoo.com (Bing Liu)

计量

出版历程

目录