胰腺早期发育及终末分化细胞重编程为胰岛β细胞的研究进展

doi:10.3724/SP.J.1005.2014.0511

遗传 ›› 2014, Vol. 36 ›› Issue (6): 511-518.doi: 10.3724/SP.J.1005.2014.0511

• 综述 • 下一篇

胰腺早期发育及终末分化细胞重编程为胰岛β细胞的研究进展

曹明君¹, 董焕生², 潘庆杰¹, 王红军¹, 董晓³

1. 青岛农业大学动物科技学院, 青岛 266109;
2. 美国南卡莱罗那医学院, 美国查尔斯顿 29425;
3. 青岛农业大学生命科学学院, 青岛 266109

收稿日期:2013-11-05 修回日期:2014-01-06 出版日期:2014-06-20 发布日期:2014-05-28
通讯作者: 董晓,博士,副教授,研究方向：生殖生理。E-mail:1163553518@qq.com E-mail:caomingjun19881112@163.com
作者简介:曹明君,硕士研究生,专业方向：动物生殖发育与基因工程。E-mail:caomingjun19881112@163.com
基金资助:
青岛农业大学高层次人才科研基金(编号：631114)资助

Progress in early pancreas development and reprogramming of terminally differentiated cells into β cells

Mingjun Cao¹, Huansheng Dong², Qingjie Pan¹, Hongjun Wang¹, Xiao Dong³

1. College of Animal Science, Qingdao Agricultural University, Qingdao 266109, China;
2. Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA;
3. College of Life Science, Qingdao Agricultural University, Qingdao 266109, China

Received:2013-11-05 Revised:2014-01-06 Online:2014-06-20 Published:2014-05-28

摘要/Abstract

摘要：

1型糖尿病是一种由于自体免疫细胞破坏分泌胰岛素的β细胞而引起胰岛素绝对缺乏的自体免疫病。疾病患者需要依靠外源性途径来补给胰岛素, 但胰岛素注射治疗不能根治病症, 也不能有效地预防糖尿病并发症。多能性干细胞以及体细胞重编程产生胰岛素分泌细胞为根治1型糖尿病提供了可能。编程性的细胞能被用来进行移植治疗和药物筛选, 为1型糖尿病的治疗带来了新的希望。当前, 通过相关转录调节因子重编程终末分化细胞为胰岛β细胞已经取得了很大进展。文章对胰腺早期发育、胰腺相关转录调控因子及目前利用终末分化细胞重编程产生胰岛β细胞的研究内容进行了综述。

关键词: 糖尿病, 胰岛β细胞, 胰腺相关转录因子, 重编程

Abstract:

Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the immune system attacks insulin-secreting β cells, thus leading to an absolute deficiency of insulin. Patients must rely on exogenous insulin, which cannot effectively prevent diabetes complications. Generation of insulin-secreting cells by reprogramming of pluripotent stem cells or somatic cells is a potential approach for the treatment of T1DM. These cells can be used for cell therapy and drug screening, and may eventually provide a cure for the disease. Significant progress has been made in generating insulin-secreting cells through the expression of β cell specific transcription factors in stem cells or somatic cells. In this review, we summarize recent research progress in early pancreas development, β cell specific transcription factors and reprogramming of terminally differentiated cells into β cells.

Key words: type 1 diabetes, &beta, cell generation, pancreatic transcription factor, cell reprogramming

曹明君, 董焕生, 潘庆杰, 王红军, 董晓. 胰腺早期发育及终末分化细胞重编程为胰岛β细胞的研究进展[J]. 遗传, 2014, 36(6): 511-518.

Mingjun Cao, Huansheng Dong, Qingjie Pan, Hongjun Wang, Xiao Dong. Progress in early pancreas development and reprogramming of terminally differentiated cells into β cells[J]. HEREDITAS(Beijing), 2014, 36(6): 511-518.

参考文献

[1]Golosow N, Grobstein C. Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev Biol, 1962, 4(2): 242-255.
[2]Wessells NK, Cohen JH. Early pancreas organogenesis: morphogenesis, tissue interactions, and mass effects. Dev Biol, 1967, 15(3): 237-270.
[3]Tremblay KD, Zaret KS. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol, 2005, 280(1): 87-99.
[4]Franklin V, Khoo PL, Bildsoe H, Wong N, Lewis S, Tam PP. Regionalisation of the endoderm progenitors and morphogenesis of the gut portals of the mouse embryo. Mech Dev, 2008, 125(7): 587-600.
[5]Lewis SL, Tam PPL. Definitive endoderm of the mouse embryo: formation, cell fates, and morphogenetic function. Dev Dyn, 2006, 235(9): 2315-2329.
[6]Zhao H, Han D, Dawid IB, Pieler T, Chen Y. Homeo-protein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos. Proc Nat Acad Sci USA, 2012, 109(22): 8594-8599.
[7]Kim SK, Hebrok M, Melton DA. Notochord to endoderm signaling is required for pancreas development. Development, 1997, 124(21): 4243-4252.
[8]Edlund H. Pancreatic organogenesis-developmental mechanisms and implications for therapy. Nature Rev Genet, 2002, 3(7): 524-532.
[9]Deltour L, Leduque P, Paldi A, Ripoche MA, Dubois P, Jami J. Polyclonal origin of pancreatic islets in aggregation mouse chimaeras. Development, 1991, 112(4): 1115- 1121.
[10]Herrera PL. Adult insulin-and glucagon-producing cells differentiate from two independent cell lineages. Develo-pment, 2000, 127(11): 2317-2322.
[11]Jensen J, Heller RS, Funder-Nielsen T, Pedersen EE, Lindsell C, Weinmaster G, Madsen OD, Serup P. Independent development of pancreatic alpha-and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes, 2000, 49(2): 163-176.
[12]Stafford D, Prince VE. Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol, 2002, 12(14): 1215-1220.
[13]Chen YL, Pan FC, Brandes N, Afelik S, Solter M, Pieler T. Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus. Dev Biol, 2004, 271(1): 144-160.
[14]Hald J, Hjorth JP, German MS, Madsen OD, Serup P, Jensen J. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol, 2003, 260(2): 426-437.
[15]Martin M, Gallego-Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, Dolle P, Gradwohl G. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Dev Biol, 2005, 284(2): 399-411.
[16]Molotkov A, Molotkova N, Duester G. Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal endodermal pancreas development. Dev Dyn, 2005, 232(4): 950-957.
[17]Wells JM, Melton DA. Early mouse endoderm is patterned by soluble factors from adjacent germ layers. Development, 2000, 127(8): 1563-1572.
[18]Hebrok M, Kim SK, Melton DA. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev, 1998, 12(11): 1705-1713.
[19]Pictet R, Rutter W. Development of the embryonic pancreas. In: Steiner DF, Frenkel N, eds. Handbook in Physiology. Vol 1. Baltimore MD: Williams & Wilkins, 1972: 25-66.
[20]Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science, 2001, 294(5542): 564-567.
[21]Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS. Mice lacking the homeodomain transcription factor Nkx 2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development, 1998, 125(12): 2213-2221.
[22]Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development. Proc Natl Acad Sci USA, 2004, 101(9): 2924-2929.
[23]Holland AM, Hale MA, Kagami H, Hammer RE, MacDonald RJ. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci USA, 2002, 99(19): 12236-12241.
[24]Fujitani Y, Fujitani S, Boyer DF, Gannon M, Kawaguchi Y, Ray M, Shiota M, Stein RW, Magnuson MA, Wright CV. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev, 2006, 20(2): 253-266.
[25]Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA, 2000, 97(4): 1607-1611.
[26]Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3 positive cells are islet progenitors and are distinct from duct progenitors. Development, 2002, 129(10): 2447-2457.
[27]Wang S, Jensen JN, Seymour PA, Hsu W, Dor Y, Sander M, Magnuson MA, Serup P, Gu G. Sustained Neurog3expres-sion in hormone-expressing islet cells is required for endocrine maturation and function. Proc Natl Acad Sci USA, 2009, 106(24): 9715-9720.
[28]Aramata S, Han SI, Kataoka K. Roles and regulation of transcription factor MafA in islet beta-cells. Endocr J, 2007, 54(5): 659-666.
[29]Artner I, Hang Y, Mazur M, Yamamoto T, Guo M, Lindner J, Magnuson MA, Stein R. MafA and MafB regulate genes critical to β-cells in a unique temporal manner. Diabetes, 2010, 59(10): 2530-2539.
[30]He KH, Juhl K, Karadimos M, El Khattabi I, Fitzpatrick C, Bonner-Weir S, Sharma A. Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA. Dev Biol, 2014, 385(1): 2-12.
[31]Bhushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R. Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development, 2001, 128(24): 5109-5117.
[32]Miralles F, Lamotte L, Couton D, Joshi RL. Interplay between FGF10 and Notch signalling is required for the self-renewal of pancreatic progenitors. Int J Dev Biol, 2006, 50(1): 17.
[33]Tennant BR, Islam R, Kramer MM, Merkulova Y, Kiang RL, Whiting CJ, Hoffman BG. The Transcription Factor Myt3 Acts as a Pro-Survival Factor in β-cells. PloS ONE, 2012, 7(12): e51501.
[34]Huang PY, He ZY, Ji SY, Sun HW, Xiang D, Liu CC, Hu YP, Wang X, Hui LJ. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature, 2011, 475(7356): 386-389.
[35]Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell, 2010, 142(3): 375-386.
[36]Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4): 663-676.
[37]Zhou Q, Melton DA. Extreme makeover: converting one cell into another. Cell Stem Cell, 2008, 3(4): 382-388.
[38]Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature, 2008, 455(7213): 627-632.
[39]Hesselson D, Anderson RM, Stainier DYR. Suppression of Ptf1a activity induces acinar-to-endocrine conversion. Curr Biol, 2011, 21(8): 712-717.
[40]Furuya F, Shimura H, Asami K, Ichijo S, Takahashi K., Kaneshige M, Oikawa Y, Aida K, Endo T, Kobayashi T. Ligand-bound thyroid hormone receptor contributes to reprogramming of pancreatic Acinar cells into insulin- producing cells. J Biol Chem, 2013, 288(22): 16155-16166.
[41]Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into α and subsequently β Cells. Cell, 2009, 138(3): 449-462.
[42]Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature, 2010, 464(7292): 1149-1154.
[43]Yang YP, Thorel F, Boyer DF, Herrera PL, Wright CV. Context-specific α-to-β-cell reprogramming by forced Pdx1 expression. Genes Dev, 2011, 25(16): 1680-1685. [44]Bramswig NC, Everett LJ, Schug J, Dorrell C, Liu C, Luo Y, Streeter PR, Naji A, Grompe K, Kaestner KH. Epigenomic plasticity enables human pancreatic α to β cell reprogramming. J Clin Invest, 2013, 123(3): 1275-1284.
[45]Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N, Karasik A. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin- induced hyperglycemia. Nature Med, 2000, 6(5): 568-572.
[46]Kaneto H, Nakatani Y, Miyatsuka T, Matsuoka TA, Matsuhisa M, Hori M, Yamasaki Y. PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes, 2005, 54(4): 1009-1022.
[47]Song YD, Lee EJ, Yashar P, Pfaff LE, Kim SY, Jameson JL. Islet cell differentiation in liver by combinatorial expression of transcription factors neurogenin-3, BETA2, and RIPE3b1. Biochem Biophys Res Commun, 2007, 354(2): 334-339.
[48]Motoyama H, Ogawa S, Kubo A, Miwa S, Nakayama J, Tagawa Y, Miyagawa S. In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. Biochem Biophys Res Commun, 2009, 385(1): 123-128.
[49]Talchai C, Xuan SH, Kitamura T, DePinho RA, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet, 2012, 44(4): 406-412.
[50]Lee J, Sugiyama T, Liu Y, Wang J, Gu X, Lei J, Markmann JF, Miyazaki S, Miyazaki J, Szot GL, Bottino R, Kim SK. Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells. Elife, 2013, 19(2): e00940.
[51]Wang Q, Wang H, Sun Y, Li SW, Donelan W, Chang LJ Jin S, Terada N, Cheng H, Reeves W, Yang LJ. Reprogrammed pancreatic progenitor-like intermediate state of hepatic cells is more susceptible to pancreatic beta cell differentiation. J Cell Sci, 2013, 126(Pt 16): 3638-3648.
[52]Swales N, Martens GA, Bonné S, Heremans Y, Borup R, Van de Casteele M, Ling Z, Pipeleers D, Ravassard P, Nielsen F, Ferrer J, Heimberg H. Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming. PloS ONE, 2012, 7(5): e37055.
[53]Dave SD, Vanikar AV, Trivedi HL. In-vitro generation of human adipose tissue derived insulin secreting cells: up-regula-tion of Pax-6, Ipf-1 and Isl-1. Cytotechnology, 2014, 66(2): 299-307.
[54]Katz LS, Geras-Raaka E, Gershengorn MC. Reprogramming adult human dermal fibroblasts to islet-like cells by epigenetic modification coupled to transcription factor modulation. Stem Cells Dve, 2013, 22(18): 2551-2560.
[55]Lima MJ, Muir KR, Docherty HM, Drummond R, McGowan NW, Forbes S, Heremans Y, Houbracken I, Ross JA, Forbes SJ, Ravassard P, Heimberg H, Casey J, Docherty K. Suppression of epithelial-to-mesenchymal transitioning enhances ex vivo reprogramming of human exocrine pancreatic tissue toward functional insulin- producing β-like cells. Diabetes, 2013, 62(8): 2821-2833.

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胰腺早期发育及终末分化细胞重编程为胰岛β细胞的研究进展

Progress in early pancreas development and reprogramming of terminally differentiated cells into β cells

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