当前位置: X-MOL 学术Skelet. Muscle › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
In remembrance of David Yaffe
Skeletal Muscle ( IF 5.3 ) Pub Date : 2020-10-24 , DOI: 10.1186/s13395-020-00246-1
Margaret Buckingham 1 , Eldad Tzahor 2
Affiliation  

The muscle community is mourning the loss of David Yaffe, emeritus professor at the Weizmann Institute of Science in Israel, who died at the beginning of July. His pioneering work on muscle cell biology played a major role in founding the modern field of myogenesis.

David was born in 1929 in Tel Aviv. He was passionate about the nature of life and focussed his studies on biology and agriculture. However in 1948, he put aside his academic training to join the Palmach, the underground military organisation that fought for the establishment of an independent state of Israel. MB remembers how he regarded her with some suspicion as a representative of the enemy colonial power until he realised that her Scottish origins meant that her ancestors had also fought the English for their freedom! David was a firm believer in the principles of the founding fathers of Israel and lived all his life on a kibbutz, with his wife and family.

In 1952 he started his M.Sc. studies in Biology at the Hebrew University of Jerusalem and after graduating went on to do a Ph.D. with Michael Feldman in the Cell Biology department of the Weizmann Institute. In 1961, he began his career there as an independent researcher. Apart from a sabbatical year in Robert Schimke’s laboratory at Stanford, he spent his entire career in the Weizmann Institute - over six decades.

Already at the onset of his research career, David realised the need for a system that would permit the study of developmental processes outside the embryo. He recognised the potential of skeletal muscle where muscle precursor cells, myoblasts, are able to differentiate and fuse together to form muscle fibers. The morphological distinction between mononucleated myoblasts and multinucleated fibers makes it possible to physically separate them, with the possibility of culturing the myoblasts. This culture system was being developed with chick muscle; David’s major contribution was to develop it using mammalian cells, first with primary cultures obtained from newborn rat muscle where he showed that proliferating myoblasts would grow as a monolayer in culture and that, when grown in a medium that was less rich in growth factors, these cells would differentiate into muscle fibers, thus demonstrating their intrinsic capacity to maintain muscle identity.

He went on to develop muscle cell lines, first from rat, such as the L6 line (isolated in his lab during the Six-Day War in 1967) [1, 2] and then, 10 years later, from mouse muscle. Based on his experimental observations of muscle cell behaviour, he developed conceptually important views about cell differentiation and tissue identity. He communicated his muscle cell expertise and made his cell lines available to others. The C2 mouse muscle line [3] and its subclone C2C12, has provided, and continues to provide, a major tool for many researchers working on myogenesis.

The Yaffe lab went on to characterise the molecular changes that occurred at the time of differentiation, in terms of the synthesis of muscle contractile proteins and of their messenger RNAs. It is hard to imagine this now, but prior to the advent of DNA cloning, it was only possible to follow radioactive labelled RNA [4] and to identify the presence of specific messenger RNAs by in vitro translation followed by SDS gel analysis of muscle contractile proteins [5]. In the 1970s, MB, working in François Gros’ lab at the Pasteur Institute in Paris, was also carrying out this type of analysis on muscle cell cultures. She remembers well David’s help with setting up the culture system, and also his interest in comparing results. There was a tinge of competition between the labs, but for David the science always came first. Subsequently with cloned probes [6] it became possible to look precisely at messenger RNAs and the transcriptional changes that took place at the time of differentiation [7]. MB began to focus on myogenesis in vivo using the mouse embryo, while the Yaffe lab continued to make important contributions with the in vitro model of myoblast culture.

Further reinforcing their findings on transcriptional regulation, the Yaffe lab demonstrated that DNAase1 hypersensitivity of muscle genes correlates with their expression at the time of cell fusion [8]. They also characterised muscle contractile protein genes [9] and their chromosomal location [10] and went on to look at their regulation [11]. In addition to their work on the transcriptional control of muscle cell differentiation, the Yaffe lab also examined the cell biology of the system and provided early insights into the manipulation of fusion and differentiation, for example by altered Ca2+ levels [12].

In a later phase of his research, David with Uri Nudel became interested in the Dystrophin gene which, when mutated, leads to Duchenne Muscular Dystrophy. In addition to its expected expression in differentiated myogenic cell cultures, they also showed that the gene is expressed in the brain [13]. They went on to characterise the promoters involved [14]. They also identified other transcripts from the Dystrophin gene and notably the Dp17 transcript controlled by a non-muscle specific promoter [15], which they then characterised functionally [16].

After his “retirement” David continued to be scientifically active, participating in work on Dp17 and Utrophin and also pursuing an interest in the stem cell properties of muscle cells, as well as in their manipulation to promote tissue regeneration, as evidenced by a paper published in his nintieth year [17].

In addition to his own research contributions, David Yaffe had major impact in federating the myogenesis research community. He understood the importance of informal communication of experimental results and ideas between the initially small number of researchers in the world working in what was then an emerging field. To promote this, he organised the first workshop on the subject in 1975 at the kibbutz of Shoresh near Jerusalem. This was followed by a second meeting there in 1980, where the strong personalities of Howard Holtzer and Irvin Konigsberg, together with David the great men of muscle cell culture, led to clashes of opinion, which David managed to deflect from confrontation to constructive discussion. In the following years, David organised other myogenesis meetings, notably in Ein Gedi. They were memorable for the science and also for what David showed us of the history and natural beauty of Israel. This tradition of international workshops supported by EMBO, initiated by David, and subsequently organised in many European countries, continues today to the great benefit of a now much larger research community interested in muscle formation and regeneration. The last such meeting where David was present was at the Weizmann Institute in 2016. He was invited, as an honoured participant, to give an evening talk. He spoke of his beloved muscle cells but also read poems he had written, translated from Hebrew, with accompanying photographs of the local countryside and its birds and flowers.

David Yaffe was passionately interested in science, and loved to discuss scientific ideas. He was tenacious and sometimes irrascible, but always true to his ideal of the pursuit of knowledge. As an experimental scientist he was rigorous and cautious about drawing rapid conclusions. When he published results they were well verified and the interpretation reliable. He was kind and encouraging to young scientists and welcomed newcomers to the field. In addition to his scientific interests, David was very knowledgeable about the archaeology, history and natural history of Israel. He was also interested in art and would try to combine a visit to an exhibition with a scientific trip abroad. Prized catalogues would be taken back to be read before they were given to the kibbutz library. David lived most of his adult life in the Kibbutz Givat Brener, a collective social community near Rehovot, that was traditionally based on agriculture. He was passionate about certain plants and special fruit trees that he grew in his garden. In addition to his remarkable scientific legacy, he leaves behind his family, his wife Ruth, three children and nine grandchildren.

When ET informed the myogenic community of David’s death, many colleagues wrote tributes to his memory. Extracts from some of these are presented here. Stephen Tapscott (Fred Hutchinson Cancer Research Center, Seattle) emphasises David’s conceptually important contribution to understanding lineage commitment, with the muscle cell systems he developed. He cites key findings in the 1960s – “the specificity of myogenic fusion between muscle cells and not other cell types; the irreversibility or “stability” of muscle differentiation and its implications for cancer; the retention of myogenic differentiation potential during prolonged myoblast replication in culture”. In addition to these early scientific insights, the cell lines that David established provided a valuable tool for many investigators. Michael Rudnicki (Ottawa Hospital Research Institute) wrote “David was without question one of the fathers of the modern myogenesis field. He was a gifted experimentalist whose many contributions form the foundation of our area of study. Notable was his derivation of C2 cells which facilitated and accelerated the cell and molecular investigation of myogenesis and continued to do so to this day.” Eric Olson (University of Texas, Southwestern Medical Center, Dallas) also emphasises this contribution “Among his many achievements was the establishment of the C2 cell line which enabled the discovery and analysis of MyoD, MEF2 and other myogenic factors and elucidation of the mechanisms of muscle gene regulation.” Andrew Lassar (Harvard Medical School) underlines the importance of this cell line for his discovery of MyoD, “In my own case the phenotypic stability of C2C12 cells (derived C2 cells) provided a great reality check to ensure that the search for a muscle determinant (i.e. MyoD) in azacytidine–induced 10T1/2 myoblasts (which displayed great phenotypic variation) would have some physiological relevance.”

The importance for the field of the myogenesis meetings that David initiated was also highlighted, with memories of the first meetings in Israel. Frank Stockdale (Stanford University) wrote “Because of David, the early meetings at Shoresh and elsewhere established Israel as a central facilitator for transfer of information, collaboration, and the social-scientific structure so important in our field. David tirelessly fostered these and the conferences that subsequently took place around the world. We are indebted to David for this, because without his efforts all of us would have had a harder time developing our careers”. Helen Blau (Stanford University) recalled “David Yaffe gave me my first big opportunity to give a talk at an international muscle meeting he organised in Shoresh, Israel. There were four women speakers, which was revolutionary at that time. That meeting made a deep impression on me – and launched me in the field.” She also comments “.. during the meeting we hiked the Wadi Qelt in spring, amidst wild flowers in full bloom, a miracle of beauty..” . Steve Hauschka (University of Washington Medical School, Seattle) adds “My fondest Shoresh memory is David offering to lead me into a small nearby forest to see wild Cyclamen plants blooming. I don’t recall his exact words, but our walk became akin to a pilgrimage for David as the delicate flowers were in some way enshrined in memories of his youth and the 1948 conflict – perhaps the contrast of wartime horrors and the Cyclamen’s enduring peaceful beauty”.

Following on from Helen Blau’s comment, others also stressed David’s encouragement of young researchers. Simon Hughes (MRC/King’s College, London) wrote “David was always an enthusiast and always happy to chat with any young and unknown postdoc whenever he got the chance. To me, he helped define the warmth and collegial nature of the myogenesis field. Many young scientists need the kind of encouragement he gave.” Also David Sassoon (UCSF and VA Hospital, San Francisco; INSERM PARCC, Paris) wrote “He was able to critique work without being condescending and at meetings would spend much time with students at their posters and with young colleagues just starting out in their professional lives.” Mary Baylies (Sloan Kettering Institute, New York) adds to this “I was scheduled to give a talk (my first!) at a Myogenesis meeting. After the talk David sought me out. He let me know that he was sceptical at the beginning of my talk but at the end he was convinced – both of the use of Drosophila as a model to dissect myogenesis and my ability to give a talk! … His wonderful presence and ability to reach out to junior colleagues in the field created a great atmosphere in our community.”

A final comment cited here came from Barbara Wold (California Institute of Technology, Pasadena) on David’s personality and capacity to attract newcomers to the field. “My first thought is of David as a wonderful, stubborn, positive force for the entire field. He leaves a lasting legacy that flows from his specific science contributions and also from his force of personality. His curiosity and interest never flagged through the decades. He was intellectually and personally gracious, and especially encouraging of scientists newly interested in myogenesis - whatever their age or career stage. A scientific argument with David was the fun kind of argument from which I usually learned something - win, lose, or draw. He was welcoming of people like me and my students who arrived as newcomers from other fields and scientific traditions. We were not treated as strangers - but rather as new recruits into the myogenesis brigade. In this and many other ways, David helped to build a vibrant and always evolving community.”

Other tributes and reminiscences about David Yaffe, mostly from previous collaborators who had worked in his lab, have been assembled by Zippora Yablonka-Reuveni (University of Washington School of Medicine, Seattle) and can be found at:

Yablonka-Reuveni, Z., Stockdale, F., Nudel, U., Israeli, D., Blau, H. M., Shainberg, A., Neuman, S., Kessler-Icekson, G., Meghid Krull, E., Paterson, B., Saxel Fuchs, O., Greenberg, D., Sarig, R., Halevy, O., Ozawa, E., & Katcoff, D. J. (2020). Farewell to Professor David Yaffe – A Pillar of the Myogenesis Field. European Journal of Translational Myology. https://doi.org/10.4081/ejtm.0.9306

  1. 1.

    Yaffe D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci U S A. 1968;61:477–83. https://doi.org/10.1073/pnas.61.2.477.

    Article PubMed PubMed Central CAS Google Scholar

  2. 2.

    Richler C, Yaffe D. The in vitro cultivation and differentiation capacities of myogenic cell lines. Dev Biol. 1970;23:1–22. https://doi.org/10.1016/s0012-1606(70)80004-5.

    Article PubMed CAS Google Scholar

  3. 3.

    Yaffe D, Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 1977;270(5639):725–7. https://doi.org/10.1038/270725a0.

    Article PubMed CAS Google Scholar

  4. 4.

    Yaffe D, Fuchs S. Autoradiographic study of the incorporation of uridine-3H during myogenesis in tissue culture. Dev Biol. 1967;15:33–50. https://doi.org/10.1016/0012-1606(67)90004-8.

    Article PubMed CAS Google Scholar

  5. 5.

    Yablonka Z, Yaffe D. Synthesis of polypeptides with the properties of myosin light chains directly by RNA extracted from muscle cultures. Proc Natl Acad Sci U S A. 1976;73:4599–603. https://doi.org/10.1073/pnas.73.12.4599.

    Article PubMed PubMed Central CAS Google Scholar

  6. 6.

    Katcoff D, Nudel U, Zevin-Sonkin D, Carmon Y, Shani M, Lehrach H, Frischauf AM, Yaffe D. Construction of recombinant plasmids containing rat muscle actin and myosin light chain DNA sequences. Proc Natl Acad Sci U S A. 1980;77:960–4. https://doi.org/10.1073/pnas.77.2.960.

    Article PubMed PubMed Central CAS Google Scholar

  7. 7.

    Zevin-Sonkin D, Yaffe D. Accumulation of muscle-specific RNA sequences during myogenesis. Dev Biol. 1980;74:326–34. https://doi.org/10.1016/0012-1606(80)90434-0.

    Article PubMed CAS Google Scholar

  8. 8.

    Carmon Y, Czosnek H, Nudel U, Shani M, Yaffe D. DNAase I sensitivity of genes expressed during myogenesis. Nucleic Acids Res. 1982;10:3085–98. https://doi.org/10.1093/nar/10.10.3085.

    Article PubMed PubMed Central CAS Google Scholar

  9. 9.

    Zakut R, Shani M, Givol D, Neuman S, Yaffe D, Nudel U. Nucleotide sequence of the rat skeletal muscle actin gene. Nature. 1982;298(5877):857–9. https://doi.org/10.1038/298857a0.

    Article PubMed CAS Google Scholar

  10. 10.

    Czosnek H, Nudel U, Shani M, Barker PE, Pravtcheva DD, Ruddle FH, Yaffe D. The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different mouse chromosomes. EMBO J. 1982;1:1299–305.

    Article CAS Google Scholar

  11. 11.

    Melloul D, Aloni B, Calvo J, Yaffe D, Nudel U. Developmentally regulated expression of chimeric genes containing muscle actin DNA sequences in transfected myogenic cells. EMBO J. 1984;3:983–90.

    Article CAS Google Scholar

  12. 12.

    Shainberg A, Yagil G, Yaffe D. Control of myogenesis in vitro by Ca2+ concentration in nutritional medium. Exp Cell Res. 1969;58:163–7. https://doi.org/10.1016/0014-4827(69)90127-x.

    Article PubMed CAS Google Scholar

  13. 13.

    Nudel U, Robzyk K, Yaffe D. Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain. Nature. 1988;331(6157):635–8. https://doi.org/10.1038/331635a0.

    Article PubMed CAS Google Scholar

  14. 14.

    Barnea E, Zuk D, Simantov R, Nudel U, Yaffe D. Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells. Neuron. 1990;5:881–8. https://doi.org/10.1016/0896-6273(90)90348-j.

    Article PubMed CAS Google Scholar

  15. 15.

    Lederfein D, Levy Z, Augier N, Mornet D, Morris G, Fuchs O, Yaffe D, Nudel U. A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. Proc Natl Acad Sci U S A. 1992;89:5346–50. https://doi.org/10.1073/pnas.89.12.5346.

    Article PubMed PubMed Central CAS Google Scholar

  16. 16.

    Greenberg DS, Sunada Y, Campbell KP, Yaffe D, Nudel U. Exogenous Dp71 restores the levels of dystrophin associated proteins but does not alleviate muscle damage in mdx mice. Nat Genet. 1994;8:340–4. https://doi.org/10.1038/ng1294-340 PMID: 7894483.

    Article PubMed CAS Google Scholar

  17. 17.

    Guy R, Grynspan F, Ben-Zur T, Panski A, Lamdan R, Danon U, Yaffe D, Offen D. Human muscle progenitor cells overexpressing neurotrophic factors improve neuronal regeneration in a sciatic nerve injury mouse model. Front Neurosci. 2019;13:151. https://doi.org/10.3389/fnins.2019.00151.

    Article PubMed PubMed Central Google Scholar

Download references

Affiliations

  1. CNRS UMR3738, Department of Developmental and Stem Cell Biology, Pasteur Institute, Paris, France

    Margaret Buckingham

  2. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

    Eldad Tzahor

Authors
  1. Margaret BuckinghamView author publications

    You can also search for this author in PubMed Google Scholar

  2. Eldad TzahorView author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ET and MB wrote this text together. The authors read and approved the final manuscript.

Corresponding authors

Correspondence to Margaret Buckingham or Eldad Tzahor.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

Verify currency and authenticity via CrossMark

Cite this article

Buckingham, M., Tzahor, E. In remembrance of David Yaffe. Skeletal Muscle 10, 31 (2020). https://doi.org/10.1186/s13395-020-00246-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/s13395-020-00246-1



中文翻译:

为了纪念大卫·雅菲

肌肉团体正在哀悼以色列魏兹曼科学研究所名誉教授大卫·雅夫(David Yaffe)的逝世,他于7月初去世。他在肌肉细胞生物学方面的开创性工作在建立现代肌生成领域中发挥了重要作用。

David于1929年出生在特拉维夫。他对生命的本质充满热情,并将研究重点放在生物学和农业上。但是,在1948年,他放弃了学术训练,加入了为建立独立的以色列国而奋斗的地下军事组织Palmach。MB记得他曾以某种怀疑的态度将她视为敌对殖民力量的代表,直到他意识到她的苏格兰血统意味着她的祖先也为自由而与英军作战!大卫坚信以色列开国元勋的原则,一生与妻子和家人一起生活在集体农庄中。

1952年,他开始攻读硕士学位。在耶路撒冷希伯来大学攻读生物学,毕业后继续攻读博士学位。与魏兹曼研究所细胞生物学系的迈克尔·费尔德曼(Michael Feldman)合作。1961年,他以一名独立研究员的身份开始了他的职业生涯。除了在斯坦福大学的罗伯特·席姆克(Robert Schimke)的实验室度过了休假的一年之外,他的整个职业生涯都花在了魏兹曼学院(Weizmann Institute)上-长达六十年。

David在他的研究生涯开始之初,就已经意识到需要一种系统来研究胚胎以外的发育过程。他认识到骨骼肌的潜力,其中肌肉前体细胞(成肌细胞)能够分化并融合在一起形成肌肉纤维。单核成肌细胞和多核纤维之间的形态学区别使得可以将它们物理分离,并有可能培养成肌细胞。这种培养系统是用雏鸡肌肉开发的。David的主要贡献是利用哺乳动物细胞开发了这种动物,首先是从新生大鼠肌肉中获得了原代培养物,他证明了增殖的成肌细胞会在培养物中以单层的形式生长,并且当在生长因子含量较低的培养基中生长时,

他继续从大鼠中开发肌肉细胞系,例如L6系(1967年六日战争期间在他的实验室中分离出)[1、2],然后在10年后从小鼠肌肉中开​​发。根据他对肌肉细胞行为的实验观察,他对细胞分化和组织特性提出了概念上重要的观点。他传达了自己在肌肉细胞方面的专业知识,并向他人公开了他的细胞系。C2小鼠肌肉细胞系[3]及其亚克隆C2C12,已经为并将继续为许多从事肌发生研究的研究人员提供了主要工具。

Yaffe实验室继续根据肌肉收缩蛋白及其信使RNA的合成来表征分化时发生的分子变化。现在很难想象,但是在DNA克隆出现之前,只能追踪放射性标记的RNA [4],并通过体外翻译,然后通过SDS凝胶分析肌肉收缩来鉴定特定信使RNA的存在。蛋白质[5]。在1970年代,MB在巴黎巴斯德研究所的FrançoisGros实验室工作,也对肌肉细胞培养进行了此类分析。她记得大卫在建立文化体系方面的帮助,以及他对比较结果的兴趣。实验室之间存在着竞争的色彩,但是对于大卫来说,科学始终是第一位的。随后,使用克隆的探针[6],可以精确查看信使RNA和分化时发生的转录变化[7]。MB开始关注使用小鼠胚胎的体内肌发生,而Yaffe实验室继续为成肌细胞培养的体外模型做出重要贡献。

Yaffe实验室进一步证实了他们在转录调节方面的发现,证明了肌肉基因的DNAase1超敏性与其在细胞融合时的表达相关[8]。他们还表征了肌肉收缩蛋白基因[9]及其染色体位置[10],然后继续研究其调控[11]。除了研究肌肉细胞分化的转录控制外,Yaffe实验室还检查了系统的细胞生物学,并为融合和分化的操纵提供了早期见识,例如通过改变Ca 2+水平[12]。

在研究的后期阶段,David与Uri Nudel一起对Dystrophin基因产生了兴趣,Dystrophin基因突变后会导致Duchenne肌肉营养不良。除了在分化的成肌细胞培养物中预期表达外,他们还表明该基因在大脑中表达[13]。他们继续描述了涉及的启动子[14]。他们还从肌营养不良蛋白基因中鉴定了其他转录本,特别是由非肌肉特异性启动子控制的Dp17转录本[15],然后对其功能进行了表征[16]。

戴维(David)退休后,他继续从事科学活动,参与Dp17和Utrophin的研究,并对肌肉细胞的干细胞特性及其对促进组织再生的操纵产生了兴趣,已发表的论文证明了这一点。在他的第九年[17]。

除了他自己的研究贡献外,David Yaffe在联合组织形成研究领域也发挥了重要作用。他了解到,最初在这个新兴领域工作的全球研究人员之间,非正式交流实验结果和思想的重要性。为了促进这一点,他于1975年在耶路撒冷附近的肖尔什(Shoresh)的基布兹(Kibbutz)组织了有关该主题的第一次研讨会。随后在1980年第二次会议上,霍华德·霍尔泽(Howard Holtzer)和欧文·柯尼斯堡(Irvin Konigsberg)的坚强个性以及肌肉细胞文化的伟人戴维(David)引起了意见冲突,戴维设法将冲突从对抗转向了建设性讨论。在随后的几年中,David举办了其他肌生成会议,尤其是在Ein Gedi。他们为科学而难忘,也为大卫向我们展示了以色列的历史和自然美景而留下深刻的印象。由EMBO支持,由David发起,随后在许多欧洲国家举办的国际研讨会的传统一直延续到今天,这对于一个对肌肉形成和再生感兴趣的更大的研究团体来说是非常有益的。David上次参加这样的会议是在2016年的魏茨曼学院。作为受邀的参加者,他被邀请做一个晚上的演讲。他谈到了自己心爱的肌肉细胞,还读了自己写的诗,从希伯来语翻译而来,并附有当地乡村及其鸟类和花朵的照片。后来在许多欧洲国家组织起来,今天继续为对肌肉形成和再生感兴趣的更大得多的研究团体带来了巨大的好处。David上次参加这样的会议是在2016年的魏茨曼学院。作为受邀的参加者,他被邀请做一个晚上的演讲。他谈到了自己心爱的肌肉细胞,还读了自己写的诗,从希伯来语翻译而来,并附有当地乡村及其鸟类和花朵的照片。后来在许多欧洲国家组织起来,今天继续为对肌肉形成和再生感兴趣的更大得多的研究团体带来了巨大的好处。David上次参加这样的会议是在2016年的魏茨曼学院。作为受邀的参加者,他被邀请做一个晚上的演讲。他谈到了自己心爱的肌肉细胞,还读了自己写的诗,从希伯来语翻译而来,并附有当地乡村及其鸟类和花朵的照片。

大卫·雅菲(David Yaffe)对科学充满热情,并喜欢讨论科学思想。他很顽强,有时很顽强,但始终忠于追求知识的理想。作为实验科学家,他在得出快速结论方面非常严格和谨慎。当他发表结果时,它们得到了很好的验证,并且解释可靠。他对年轻的科学家很友善和鼓励,并欢迎该领域的新手。除科​​学兴趣外,大卫还非常了解以色列的考古,历史和自然历史。他还对艺术感兴趣,并会尝试将参观展览与科学出国旅行相结合。珍贵的目录将被取回,然后再提供给基布兹图书馆。大卫大部分成年生活都在基布兹·吉瓦特·布雷纳(Kibbutz Givat Brener)那里,雷霍沃特附近的一个集体社会​​社区,传统上以农业为基础。他对自己花园里种的某些植物和特殊果树充满热情。除了杰出的科学遗产外,他还留下了家人,妻子露丝(Ruth),三个孩子和九个孙子。

当ET向肌肉组织告知戴维的死亡时,许多同事向他的记忆致敬。这里有一些摘录。斯蒂芬·塔普斯科特(Stephen Tapscott)(西雅图弗雷德·哈钦森癌症研究中心)强调戴维在他所开发的肌肉细胞系统方面对理解血统承诺的重要概念贡献。他引用了1960年代的主要发现:“肌肉细胞而非其他细胞类型之间的肌源性融合的特异性;肌肉分化的不可逆性或“稳定性”及其对癌症的影响;延长成肌细胞在培养中的复制过程中保留成肌分化潜能”。除了这些早期的科学见解之外,David建立的细胞系为许多研究人员提供了有价值的工具。渥太华医院研究所的迈克尔·鲁德尼基(Michael Rudnicki)写道:“毫无疑问,大卫是现代肌生成领域的先驱之一。他是一位有天赋的实验家,他的许多贡献构成了我们研究领域的基础。值得注意的是,他衍生出C2细胞,从而促进并加速了细胞和分子的肌发生研究,并一直持续到今天。” 埃里克·奥尔森(Eric Olson)(得克萨斯大学,西南医学中心,达拉斯)也强调了这一贡献。“他的许多成就包括建立了C2细胞系,该细胞系能够发现和分析MyoD,MEF2和其他肌源性因子,并阐明了其中的机制。肌肉基因调控。” 哈佛医学院的安德鲁·拉萨(Andrew Lassar)强调了这种细胞系对于他发现MyoD的重要性,

还强调了大卫发起的肌生成会议领域的重要性,并记住了以色列的第一次会议。斯坦福大学的弗兰克·斯托克代尔(Frank Stockdale)写道:“由于戴维(David),在肖尔什(Shoresh)和其他地方举行的早期会议使以色列成为信息传递,合作和在我们领域如此重要的社会科学结构的中央推动者。大卫不懈地促进了这些以及随后在世界各地举行的会议。我们为此欠戴维(David),因为如果没有他的努力,我们所有人将很难发展自己的职业。” 斯坦福大学的海伦·布劳(Helen Blau)回忆说:“大卫·雅夫(David Yaffe)给了我我第一个重要的机会,在他在以色列肖尔什(Shoresh)组织的一次国际肌肉会议上发表演讲。有四位女发言人,在当时是革命性的。那次会议给我留下了深刻的印象,并让我进入了这个领域。她还评论说:“ ..在会议期间,我们在春天盛开了瓦迪古尔特山,野花盛开,这是美丽的奇迹。” 西雅图华盛顿大学医学院的史蒂夫·豪斯卡(Steve Hauschka)补充说:“我对肖尔什最美好的回忆是戴维(David)提供的引导,让我进入附近的一处小树林,看看仙客来野生植物的开花。我不记得他的确切用词,但我们的步伐就像大卫的朝圣之旅一样,因为精致的花朵以某种方式体现在对他年轻和1948年冲突的记忆中–也许是战时恐怖与仙客来持久和平的对比”。在会议期间,我们在春天盛开了野花的野花中绽放了瓦迪·凯尔特峰的美丽奇迹。” 西雅图华盛顿大学医学院的史蒂夫·豪斯卡(Steve Hauschka)补充说:“我对肖尔什最美好的回忆是戴维(David)提供的引导,让我进入附近的一处小树林,看看仙客来野生植物的开花。我不记得他的确切用词,但我们的步伐就像大卫的朝圣之旅一样,因为精致的花朵以某种方式体现在对他年轻和1948年冲突的记忆中–也许是战时恐怖与仙客来持久和平的对比”。在会议期间,我们在春天盛开了野花的野花中绽放了瓦迪·凯尔特峰的美丽奇迹。” 西雅图华盛顿大学医学院的史蒂夫·豪斯卡(Steve Hauschka)补充说:“我对肖尔什最美好的回忆是戴维(David)提供的引导,让我进入附近的一处小树林,看看仙客来野生植物的开花。我不记得他的确切用词,但我们的步伐就像大卫的朝圣之旅一样,因为精致的花朵以某种方式体现在对他年轻和1948年冲突的记忆中–也许是战时恐怖与仙客来持久和平的对比”。

继海伦·布劳(Helen Blau)的评论之后,其他人也强调了大卫对年轻研究人员的鼓励。西蒙·休斯(Simon Hughes)(伦敦MRC /国王学院)写道:“戴维一直是一个狂热者,只要有机会,他总是很乐意与任何年轻的未知博士后聊天。对我来说,他帮助定义了肌生成领域的温暖和大学性质。许多年轻的科学家需要他给予的那种鼓励。” 大卫·萨森(David Sassoon)(旧金山的UCSF和VA医院;巴黎的INSERM PARCC)写道:“他能够在不屈尊的情况下进行批判性工作,在会议上,他们会花费很多时间与海报制作者以及年轻的同事们一起开始他们的职业生涯。生活。” 纽约斯隆·凯特琳学院的玛丽·贝利斯(Mary Baylies)补充说:“我原定在Myogenesis会议上发表演讲(这是我的第一个!)。谈话结束后,大卫把我找了出来。他让我知道他在演讲开始时表示怀疑,但最后他说服了–果蝇用作剖析肌生成的模型以及我发表演讲的能力!…他出色的存在和与该领域的下级同事接触的能力为我们的社区营造了良好的氛围。”

此处引述的最后评论来自芭芭拉·沃尔德(Barbara Wold,加利福尼亚州帕萨迪纳市的技术学院)关于戴维的个性和吸引新人进入该领域的能力。“我首先想到的是戴维(David),是整个领域的一支奇,而固执的积极力量。他留下了持久的遗产,这源于他的特殊科学贡献以及他的人格力量。几十年来,他的好奇心和兴趣从未减弱。他在学术上和个人上都很客气,尤其是鼓励新近对肌生成感兴趣的科学家-无论年龄或职业阶段。与David进行科学论证是一种有趣的论点,我通常从中学到一些东西-赢,输或平。他欢迎像我这样的人和我的学生,他们是来自其他领域和科学传统的新来者。我们不被视为陌生人,而是被视为肌新生大队的新成员。通过这种方式以及许多其他方式,David帮助建立了一个充满活力且始终在不断发展的社区。”

Zippora Yablonka-Reuveni(华盛顿大学医学院,西雅图分校)汇集了有关David Yaffe的其他致敬和回忆,主要来自以前在他的实验室工作的合作者。

Yablonka-Reuveni,Z.,Stockdale,F.,Nudel,U.,Israel,D.,Blau,HM,Shainberg,A.,Neuman,S.,Kessler-Icekson,G.,Meghid Krull,E.,Paterson ,B。,萨克森·福克斯(Saxel Fuchs),O。,格林伯格(D.),萨里格(R.Sarig),哈利维(O. 告别David Yaffe教授-Myogenesis领域的支柱。欧洲转化性肌病杂志。https://doi.org/10.4081/ejtm.0.9306

  1. 1。

    Yaffe D.长时间培养成肌细胞期间保留分化潜能。美国国家科学院学报,1968; 61:477-83。https://doi.org/10.1073/pnas.61.2.477。

    文章PubMed PubMed Central CAS Google学术搜索

  2. 2。

    Richler C,YaffeD。成肌细胞系的体外培养和分化能力。Dev Biol。1970; 23:1-22。https://doi.org/10.1016/s0012-1606(70)80004-5。

    文章PubMed CAS Google学术搜索

  3. 3。

    Yaffe D,SaxelO。从营养不良的小鼠肌肉分离的成肌细胞的连续传代和分化。性质。1977; 270(5639):725-7。https://doi.org/10.1038/270725a0。

    文章PubMed CAS Google学术搜索

  4. 4。

    Yaffe D,Fuchs S.组织培养中肌生成过程中尿苷3 H掺入的放射自显影研究。Dev Biol。1967; 15:33-50。https://doi.org/10.1016/0012-1606(67)90004-8。

    文章PubMed CAS Google学术搜索

  5. 5,

    Yablonka Z,YaffeD。直接从肌肉培养物中提取的RNA合成具有肌球蛋白轻链特性的多肽。美国国家科学院学报,1976; 73:4599–603。https://doi.org/10.1073/pnas.73.12.4599。

    文章PubMed PubMed Central CAS Google学术搜索

  6. 6。

    Katcoff D,Nudel U,Zevin-Sonkin D,Carmon Y,Shani M,Lehrach H,Frischauf AM,YaffeD。构建包含大鼠肌肉肌动蛋白和肌球蛋白轻链DNA序列的重组质粒。美国国家科学院学报,1980; 77:960-4。https://doi.org/10.1073/pnas.77.2.960。

    文章PubMed PubMed Central CAS Google学术搜索

  7. 7。

    Zevin-Sonkin D,YaffeD。在肌肉形成过程中积累了肌肉特异性RNA序列。Dev Biol。1980; 74:326-34。https://doi.org/10.1016/0012-1606(80)90434-0。

    文章PubMed CAS Google学术搜索

  8. 8。

    Carmon Y,Czosnek H,Nudel U,Shani M,YaffeD。DNAase I对肌发生过程中表达的基因的敏感性。核酸研究。1982; 10:3085-98。https://doi.org/10.1093/nar/10.10.3085。

    文章PubMed PubMed Central CAS Google学术搜索

  9. 9。

    Zakut R,Shani M,Givol D,Neuman S,Yaffe D,Nudel U.大鼠骨骼肌肌动蛋白基因的核苷酸序列。性质。1982; 298(5877):857-9。https://doi.org/10.1038/298857a0。

    文章PubMed CAS Google学术搜索

  10. 10。

    Czosnek H,Nudel U,Shani M,Barker PE,Pravtcheva DD,Ruddle FH,YaffeD。编码肌肉收缩蛋白,肌球蛋白重链,肌球蛋白轻链2和骨骼肌肌动蛋白的基因位于三个不同的小鼠染色体上。EMBO J. 1982; 1:1299-305。

    文章CAS Google Scholar

  11. 11。

    Melloul D,Aloni B,Calvo J,Yaffe D,NudelU。在转染的成肌细胞中发育调控包含肌肉肌动蛋白DNA序列的嵌合基因的表达。EMBO J. 1984; 3:983–90。

    文章CAS Google Scholar

  12. 12

    Shainberg A,Yagil G,YaffeD。在营养培养基中通过Ca 2+浓度体外控制肌生成。Exp Cell水库。1969; 58:163-7。https://doi.org/10.1016/0014-4827(69)90127-x。

    文章PubMed CAS Google学术搜索

  13. 13

    Nudel U,Robzyk K,Yaffe D.在分化的成肌细胞培养物中和大脑中推定的杜兴氏肌营养不良基因的表达。性质。1988; 331(6157):635-8。https://doi.org/10.1038/331635a0。

    文章PubMed CAS Google学术搜索

  14. 14。

    Barnea E,Zuk D,Simantov R,Nudel U,Yaffe D.肌肉和脑肌营养不良蛋白基因启动子在肌肉和脑细胞中表达的特异性。神经元。1990; 5:881-8。https://doi.org/10.1016/0896-6273(90)90348-j。

    文章PubMed CAS Google学术搜索

  15. 15

    Lederfein D,Levy Z,Augier N,Mornet D,Morris G,Fuchs O,Yaffe D,NudelU。71千屈蛋白是Duchenne肌肉营养不良基因在大脑和其他非肌肉组织中的主要产物。美国国家科学院学报,1992; 89:5346-50。https://doi.org/10.1073/pnas.89.12.5346。

    文章PubMed PubMed Central CAS Google学术搜索

  16. 16。

    Greenberg DS,Sunada Y,Campbell KP,Yaffe D,NudelU。外源Dp71恢复了肌营养不良蛋白相关蛋白的水平,但并未减轻mdx小鼠的肌肉损伤。Nat Genet。1994; 8:340-4。https://doi.org/10.1038/ng1294-340 PMID:7894483。

    文章PubMed CAS Google学术搜索

  17. 17。

    Guy R,Grynspan F,Ben-Zur T,Panski A,Lamdan R,Danon U,Yaffe D,OffenD。在神经元损伤小鼠模型中,过度表达神经营养因子的人肌肉祖细胞可改善神经元再生。前神经科学。2019; 13:151。https://doi.org/10.3389/fnins.2019.00151。

    文章PubMed PubMed Central Google学术搜索

下载参考

隶属关系

  1. CNRS UMR3738,巴斯德研究所发育与干细胞生物学系,法国巴黎

    玛格丽特·白金汉

  2. 以色列雷霍沃特魏兹曼科学研究所分子细胞生物学系

    埃尔达·扎霍尔

s
  1. 玛格丽特·白金汉查看作者出版物

    您也可以在PubMed Google学术搜索中搜索该作者 

  2. Eldad Tzahor查看作者出版物

    您也可以在PubMed Google学术搜索中搜索该作者 

会费

ET和MB一起写了这段文字。作者阅读并批准了最终手稿。

通讯作者

对应于Margaret Buckingham或Eldad Tzahor。

利益争夺

作者宣称他们没有竞争利益。

发行人须知

对于已发布地图和机构隶属关系中的管辖权主张,Springer Nature保持中立。

开放存取本文是根据知识共享署名4.0国际许可许可的,该许可允许以任何媒介或格式使用,共享,改编,分发和复制,只要您对原始作者和出处提供适当的信誉,链接到知识共享许可,并指出是否进行了更改。本文的图像或其他第三方材料包含在该文章的知识共享许可中,除非在该材料的信用栏中另有说明。如果该材料未包含在该文章的创用CC许可中,并且您的预期用途未得到法律法规的许可或超出了许可的用途,则您需要直接获得版权所有者的许可。要查看此许可证的副本,请访问http://creativecommons.org/licenses/by/4.0/。

转载和许可

通过CrossMark验证货币和真实性

引用本文

M.白金汉,Tzahor,E。纪念David Yaffe。骨骼肌 10, 31(2020)。https://doi.org/10.1186/s13395-020-00246-1

下载引文

  • 发表时间

  • DOI https //doi.org/10.1186/s13395-020-00246-1

更新日期:2020-10-27
down
wechat
bug