Charles Philippe Leblond : biography
High Resolution Autoradiography procedure continues to be used today by molecular biologists to detect RNA molecules in situ, and to study the localization of genes and DNA sequences.
Studies on the turnover of cells
Leblond used autoradiography to introduce radioactive precursors of DNA, and then examine the renewal and fate of cells of several basic tissue types. He demonstrated for the first time that most cells and tissues in the adult body undergo continued renewal. Using mathematical models and modern methods of quantitation, Leblond and his colleagues estimated with remarkable accuracy the turnover and mitotic rates of numerous cell types. He and his colleagues made fascinating discoveries that resulted in the introduction of "time dimension" to cells and tissues, opening the doors to the understanding of the cell cycle and to the identification of stem cells.
Identification of Stem Cells in Adult Organs
In the male seminiferous epithelium, studies by Leblond and Yves Clermont in the early 1950s had deciphered how spermatogonia gave rise to spermatocytes, which then differentiated into mature sperm cells in a specific cycle.C.P. Leblond and Y. Clermont. Definition of the stages of the cycle of the seminiferous epithelium of the rat. Ann. NY Acad. Sci. 1952, 55, 548 573.Y. Clermont and C.P. Leblond. Spermiogenesis of man, monkey, ram and other mammals as shown by the "periodic acid Schiff" technique. Am. J. Anat. 1955, 96, 229 250.
To maintain the population of spermatogonia, the seminiferous epithelium was shown to contain a population of stem cells which divided to produce differentiated cells as well as to maintain their own number. As noted in a seminal publication by Leblond, "the reappearance at each cycle of a new dormant cell which acts as the stem cell of spermatocytes is described as the ‘Stem Cell Renewal Theory’" . This article is the first one in which nests of cells dividing in an adult organ are designated as “stem cells”.Y. Clermont and C.P. Leblond. Renewal of spermatogonia in the rat testis. Am. J. Anat. 1953, 93, 475 502.
Leblond and his colleagues also found evidence for the presence of occasional adult stem cells even in tissues which are composed almost entirely of non-dividing cells. In skeletal muscle, the muscle fibers had been shown to exhibit an age-related increase in the number of nuclei.M. Enesco and C.P. Leblond. Increase in cell number as a factor in the growth of the organs and tissues of the young male rat. J. Embryol. Exp. Morphol. 1962, 20, 530 562. His studies showed that muscle satellite cells could be considered to be adult stem cells in muscle fibers.
From the studies of Leblond and his colleagues, it was concluded that the body has three types of cell populations:
- "Static cell populations", which are composed of non-dividing cells and include no adult stem cells. These populations have the "stability" formerly attributed to all cells
- "Expanding cell populations" in which small numbers of adult stem cells exist, and give rise to skeletal fiber nuclei or glial cells of the brain
- "Renewing cell populations" in which adult stem cells are an essential feature
To mark his 65th birthday in 1975, Leblond was honored at an international symposium on the existence of stem cells in adult tissues; the resulting book, Stem Cells of Renewing Cell Populations, was the first formal, comprehensive account on the subject.Cairnie A.B., Lala P.K. and D.G. Osmond. Stem Cells of renewing Cell Populations Academic Press. N.Y. 1976.
Continuous Protein Synthesis in living Cells
When Leblond and his colleagues used 14C-bicarbonate, and then 35S-labeled amino acids to investigate protein synthesis, they were astonished to find that virtually all cells in the body incorporated label.R.C. Greulich and C.P. Leblond. Radioautographic visualization of radio carbon in the organs and tissues of newborn rats following administration of C14 labeled bicarbonate. Anat. Rec. 1953, 115, 559 586.C.P. Leblond, N.B. Everett and B. Simmons. Sites of protein synthesis as shown by radioautography after administration of S35 methionine. Am. J. Anat. 1957, 101, 225 271. This led them to the conclusion, considered heretical at the time, that all cells continually synthesized proteins. This was among the first evidence to replace the Specificity concept with the idea that most cells are multipotential in their functions.