Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic展开更多
Cancer is one of the major causes of mortality in Ecuador and annually, hematological malignancies are within the top ten most common cancers. In this multicentric study, we analyzed a series of patients diagnosed wit...Cancer is one of the major causes of mortality in Ecuador and annually, hematological malignancies are within the top ten most common cancers. In this multicentric study, we analyzed a series of patients diagnosed with different hematological disorders between the years 1984 and 2012. Chromosome abnormalities were detected in 1886 (45.9%) patients. FISH and RT-PCR techniques were used in order to determine the presence of genetic rearrangements and complement conventional cytogenetics results. Using FISH and RT-PCR, positive cases were increased by 1.8% and 6.9% respec- tively. We analyzed fusion genes resulting from t(8;21), t(15;17), inv(16), t(9;22), 11q23 rearrangements, t(4;11) and t(1;19). The frequency of transcripts of some of these fusion genes was of particular interest as our results differ from studies on other populations. Specifically, the fusion gene BCR-ABL was present in the form of the b2/a2 transcript in 95% of CML patients and in the form of b3/a2 transcript in the remaining 5%. The PML-RARA fusion gene also showed a distinct pattern of transcript expression. This fusion gene exhibited the bcr2 (36%) and bcr3 (64%) transcripts, how- ever the bcr1 transcript was absent from our sample population. All cases carrying the CBFB-MYH11 fusion gene ex- hibited the F transcript. This was also of interest due to the rarity of this particular transcript worldwide. Finally all cases carrying the MLL-AF4 fusion gene displayed the e7-e8 transcript. The frequency of the subtypes of some fusion genes differ from those reported in other populations, possibly due to the particular genetic make-up of the Ecuadorian population, mostly mestizo, as well as environmental factors.展开更多
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic
文摘Cancer is one of the major causes of mortality in Ecuador and annually, hematological malignancies are within the top ten most common cancers. In this multicentric study, we analyzed a series of patients diagnosed with different hematological disorders between the years 1984 and 2012. Chromosome abnormalities were detected in 1886 (45.9%) patients. FISH and RT-PCR techniques were used in order to determine the presence of genetic rearrangements and complement conventional cytogenetics results. Using FISH and RT-PCR, positive cases were increased by 1.8% and 6.9% respec- tively. We analyzed fusion genes resulting from t(8;21), t(15;17), inv(16), t(9;22), 11q23 rearrangements, t(4;11) and t(1;19). The frequency of transcripts of some of these fusion genes was of particular interest as our results differ from studies on other populations. Specifically, the fusion gene BCR-ABL was present in the form of the b2/a2 transcript in 95% of CML patients and in the form of b3/a2 transcript in the remaining 5%. The PML-RARA fusion gene also showed a distinct pattern of transcript expression. This fusion gene exhibited the bcr2 (36%) and bcr3 (64%) transcripts, how- ever the bcr1 transcript was absent from our sample population. All cases carrying the CBFB-MYH11 fusion gene ex- hibited the F transcript. This was also of interest due to the rarity of this particular transcript worldwide. Finally all cases carrying the MLL-AF4 fusion gene displayed the e7-e8 transcript. The frequency of the subtypes of some fusion genes differ from those reported in other populations, possibly due to the particular genetic make-up of the Ecuadorian population, mostly mestizo, as well as environmental factors.
