BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

BCAS1 was one of the most enriched proteins in oligodendrocytes in the previously generated proteome database.

“We examined our previously generated proteome database for oligodendrocyte specific proteins and noticed that BCAS1 was one of the most enriched proteins in oligodendrocytes (21).”

• cites [21] Sharma K Schmitt S Bergner CG Tyanova S Kannaiyan N Manrique-Hoyos N Kongi K Cantuti L Hanisch U-K Philips M-A Rossner MJ Cell type- and brain region-resolved mouse brain proteome Nat Neurosci 2015 18 1819 1831 26523646 PMC7116867 sourcePartly supported

  The Results section describes a cell-type-resolved proteome and ranks proteins by enrichment in oligodendrocytes, supporting the identification of the previously generated database. But the passages naming enriched proteins do not mention BCAS1, and searches for BCAS1 and its expanded name found no passage establishing that it was among the most enriched. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

17.1 ± 1.9% of BCAS1+ cells displayed myelin segments with a patchy arrangement along the axons resembling intermittent myelin.

“A total of 17.1 ± 1.9% of these BCAS1+ cells displayed myelin segments with a patchy arrangement along the axons resembling the previously reported “intermittent myelin” of cortical pyramidal neurons (fig. S3B) (27).”

• cites [27] Tomassy GS Berger DR Chen H-H Kasthuri N Hayworth KJ Vercelli A Seung HS Lichtman JW Arlotta P Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex Science 2014 344 319 324 24744380 PMC4122120 sourceSupported

Older patients are likely to remain receptive to regenerative therapies.

“Thus, older patients are likely to remain receptive to regenerative therapies, which is in line with the conclusions drawn from experimental mouse models (41).”

• cites [41] Ruckh JM Zhao J-W Shadrach JL van Wijngaarden P Rao TN Wagers AJ Franklin RJM Rejuvenation of regeneration in the aging central nervous system Cell Stem Cell 2012 10 96 103 22226359 PMC3714794 sourcePartly supported

  The Discussion concludes that aged oligodendrocyte progenitor cells remain responsive to signals that promote repair and identifies them as potential targets for remyelination therapy, including in MS patients. The claim extends that conclusion from a specific CNS repair process to older patients’ receptiveness to regenerative therapies generally. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

BCAS1+ oligodendrocytes are reformed after experimental demyelination.

“BCAS1+ oligodendrocytes are reformed after experimental demyelination and found in a proportion of chronic white matter lesions of patients with multiple sclerosis (MS) even in a subset of patients with advanced disease.”

Only few (17.7 ± 4.3%) BCAS1+ myelinating oligodendrocytes expressed myelin basic protein (MBP).

“In addition, immunostainings of the somatosensory cortex of adult wild-type mice showed that BCAS1+ myelinating oligodendrocytes were only positive for MAG and negative for PLP and that only few (17.7 ± 4.3%) expressed myelin basic protein (MBP), supporting our hypothesis that these cells constitute a distinct population of oligodendrocytes (fig. S3, D to G).”

47.5 ± 3.2% of BCAS1+ cells overlapped with myelin-associated glycoprotein (MAG).

“The remaining cells were more differentiated, as shown by their reactivity with antibodies against mature oligodendrocytes such as adenomatous polyposis coli protein (76.2 ± 3.5% of overlap) (Fig. 1C; anti-adenomatous polyposis coli antibody, clone CC1) and myelin-associated glycoprotein (MAG; 47.5 ± 3.2% of overlap), a protein involved in oligodendrocyte and axon contact (Fig. 1C).”

BCAS1 is expressed in a larger population of newly formed oligodendrocytes in the somatosensory cortex at P9 and P14.

“Whereas all of the GFP+ premyelinating oligodendrocytes also showed immunoreactivity against BCAS1, most of the BCAS1+ premyelinating cells (70.5 ± 8.1% at P9 and 76.3 ± 1.7% at P14) did not express GFP, demonstrating that BCAS1 is expressed in a larger population of newly formed oligodendrocytes in the somatosensory cortex at both P9 and P14 (Fig. 2B).”

In the adult somatosensory cortex (4 months), all BCAS1+ premyelinating oligodendrocytes were negative for GFP.

“When the analysis was performed in the adult somatosensory cortex (at 4 months), we found that all BCAS1+ premyelinating oligodendrocytes were negative for GFP, suggesting that the previously identified PLP+ premyelinating oligodendrocytes constitute a subpopulation (29.5 ± 8.1% at P9,23.7 ± 1.7% at P14, and 0% at 4 months) of oligodendrocytes present only during development (Fig. 2B).”

BCAS1 expression identifies an oligodendroglial subpopulation in the mouse and human brain.

“We find that breast carcinoma amplified sequence 1 (BCAS1) expression identifies an oligodendroglial subpopulation in the mouse and human brain.”

BCAS1+ oligodendrocytes are found in a proportion of chronic white matter lesions of patients with multiple sclerosis, even in a subset of patients with advanced disease.

“BCAS1+ oligodendrocytes are reformed after experimental demyelination and found in a proportion of chronic white matter lesions of patients with multiple sclerosis (MS) even in a subset of patients with advanced disease.”

All BCAS1+ cells in the mouse corpus callosum and somatosensory cortex at P40 and 4 months were of the oligodendrocyte lineage.

“Immunofluorescence on frozen mouse tissue sections of the corpus callosum and somatosensory cortex [postnatal day 40 (P40) and 4 months] showed that all BCAS1+ cells were of the oligodendrocyte lineage, as shown bycolabeling with the lineage markers, sex-determining region Y box 10 protein (SOX10), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (Fig. 1, A and B, and fig. S2, A and B).”

In adult wild-type mouse somatosensory cortex, BCAS1+ myelinating oligodendrocytes were only positive for MAG and negative for PLP.

“In addition, immunostainings of the somatosensory cortex of adult wild-type mice showed that BCAS1+ myelinating oligodendrocytes were only positive for MAG and negative for PLP and that only few (17.7 ± 4.3%) expressed myelin basic protein (MBP), supporting our hypothesis that these cells constitute a distinct population of oligodendrocytes (fig. S3, D to G).”

A small fraction (16.5 ± 2.8%) of BCAS1+ cells were oligodendrocyte progenitor cells (NG2+).

“Immunolabeling with antibodies against neural/glial antigen 2 (NG2; a marker for oligodendrocyte progenitor cells) revealed that a small fraction (16.5 ± 2.8%) of the BCAS1+ cells were oligodendrocyte progenitor cells (Fig. 1C).”

At P14, a population of GFP+ myelinating oligodendrocytes that lacked BCAS1 expression emerged.

“However, when the analysis was performed at P14, a population of GFP+ myelinating oligodendrocytes that lacked BCAS1 expression emerged (Fig. 2, E and F), suggesting that BCAS1 expression is lost when oligodendrocytes mature into later stages of oligodendrocyte differentiation (Fig. 2, G and H).”

BCAS1+ segments ensheath axons.

“High-resolution confocal images of somatosensory cortex sections confirmed ensheathment of axons by BCAS1+ segments as shown by costaining with antibodies against a neurofilament (Fig. 2C).”

BCAS1+ segments were flanked by contactin-associated protein 1 clusters on one side (17.1 ± 1.9%) or both sides (62.2 ± 2.9%), indicating the formation of myelin sheaths.

“BCAS1+ segments were flanked by contactin-associated protein 1 clusters on one side (one paranode, 17.1 ± 1.9%) or both sides (two paranodes, 62.2 ± 2.9%), indicating the formation of myelin sheaths (Fig. 2D).”

In adult mice, no overlap between BCAS1+ and GFP+ cell populations was seen after PLP-CreERT2 labeling.

“When brain sections were analyzed by immunohistochemistry 18 days after injection, no overlap between BCAS1+ and GFP+ cell populations was seen in adult mice (fig. S3C).”

At 4 months, there was complete segregation of GFP+ and BCAS1+ myelinating oligodendrocytes.

“At 4 months, we observed a complete segregation of GFP+ and BCAS1+ myelinating oligodendrocytes (Fig. 2F).”

At P9, all GFP+ myelinating oligodendrocytes were also positive for BCAS1.

“To further analyze these cells, we used the PLP-GFP reporter mice to visualize myelinating oligodendrocytes and found that, at P9, all GFP+ myelinating oligodendrocytes were also positive for BCAS1 (Fig. 2, E and F).”

76.2 ± 3.5% of BCAS1+ cells overlapped with adenomatous polyposis coli protein (CC1).

“The remaining cells were more differentiated, as shown by their reactivity with antibodies against mature oligodendrocytes such as adenomatous polyposis coli protein (76.2 ± 3.5% of overlap) (Fig. 1C; anti-adenomatous polyposis coli antibody, clone CC1) and myelin-associated glycoprotein (MAG; 47.5 ± 3.2% of overlap), a protein involved in oligodendrocyte and axon contact (Fig. 1C).”

BCAS1+ premyelinating oligodendrocytes were found at higher densities in the somatosensory cortex of young (P40) and adult (4 and 7 months) mice compared to aged (21 months) mice.

“BCAS1+ premyelinating oligodendrocytes were also found at higher densities in the somatosensory cortex of young (P40) and adult (4 and 7 months) mice compared to aged (21 months) mice (Fig. 4A).”

No BCAS1+ cells were positive for the proliferation marker Ki67.

“On the contrary, only 3.5 ± 1.4% of the BCAS1+ cells was also positive for NG2 (Fig. 5, A and B), and no cells were positive for the proliferation marker Ki67 (fig. S11A).”

The number of EdU+/BCAS1+ premyelinating and myelinating oligodendrocytes remained stable after the chase in the cortex.

“In addition, analysis of premyelinating and myelinating oligodendrocytes individually showed that the number EdU+/BCAS1+ remained stable after the chase (fig. S8, A and B).”

BCAS1+ oligodendrocytes are found in the predicted chronological sequence of remyelination in human MS lesions.

“Thus, BCAS1+ oligodendrocytes are found in the predicted chronological sequence of remyelination in human MS lesions”

BCAS1+ oligodendrocytes are increased in the normal-appearing white matter surrounding chronic lesions with remyelination.

“BCAS1+ oligodendrocytes were also increased in the normalappearing white matter surrounding chronic lesions with remyelination (fig. S13).”

In mice but not in humans, a large fraction of BCAS1+ cells colocalize with CC1.

“In mice but not in humans, a large fraction of the BCAS1+ cells colocalized with CC1”

The number of BCAS1+ cells in the corpus callosum was similar to NG2+ oligodendrocyte progenitor cells at P40 and at 4 months.

“Quantification of the number of BCAS1+ cells in the corpus callosum revealed numbers similar to NG2+ oligodendrocyte progenitor cells at P40 and at 4 months (fig. S9A).”

BCAS1 was expressed in 85.9 ± 2.2% of the population of O4+ oligodendrocytes with arborized morphology at 3 days in vitro.

“BCAS1 was expressed in 85.9 ± 2.2% of the population of O4+ oligodendrocytes with arborized morphology at 3 days in vitro (fig. S5A).”

Only 3.5 ± 1.4% of the BCAS1+ cells was also positive for NG2.

“On the contrary, only 3.5 ± 1.4% of the BCAS1+ cells was also positive for NG2 (Fig. 5, A and B), and no cells were positive for the proliferation marker Ki67 (fig. S11A).”

BCAS1 was expressed in 86.1 ± 2.3% of O4+ oligodendrocytes with arborized morphology at 24 days in vitro in human iPSC-derived oligodendrocytes.

“We found that BCAS1 was expressed in 86.1 ± 2.3% of the O4+ oligodendrocytes with arborized morphology at 24 days in vitro (fig. S7A).”

In a mouse model of focal demyelination induced by lysolecithin injection, BCAS1+ cell density increases from days 3 to 12 after injection in the phase of most intense remyelination.

“We found that BCAS1+ cell density increased from days 3 to 12 after injection in the phase of most intense remyelination (Fig. 6, A and B).”

Incorporation of 13C-lysines into myelin proteins occurred at a higher rate in 1- and 4-month-old mice compared to 18- and 26-month-old animals.

“The incorporation of the13C-lysines into myelin proteins occurred at a higher rate in 1- and 4-month-old mice when compared to 18- and 26-month-old animals (Fig. 4B).”

BCAS1 staining of the corpus callosum of adult, 4-month-old mice showed a marked reduction of labeled cells compared to younger animals (P40).

“BCAS1 staining of the corpus callosum of adult, 4-month-old mice showed a marked reduction of labeled cells compared to younger animals (P40) (fig. S9A).”

Galactosylceramides/sulfatides (recognized by O1 and O4 immunolabeling) remain enriched in myelin sheets of differentiated cells in vitro and in vivo.

“This is in contrast to galactosylceramides/sulfatides (recognized by O1 and O4 immunolabeling), another oligodendroglial marker, which remain enriched in myelin sheets of differentiated cells in vitro (fig. S6A) and in vivo (fig. S6B).”

The number of GFP+/BCAS1+ myelinating oligodendrocytes remained stable at 6 weeks after Esco2 induction.

“Although the number of GFP+/BCAS1+ myelinating oligodendrocytes cells remained stable at 6 weeks after induction (Fig. 3G), we found a marked reduction in the number of GFP+/BCAS1+ premyelinating oligodendrocytes (reduction from 92.1 ± 3.1% in control to 29.5 ± 1.3% in the knockout; fig. S8C) and GFP+/ BCAS1+ myelinating oligodendrocytes (reduction from 97.6 ± 2.4% in control to 13.9 ± 7.3% in the”

In the human frontal cortex, BCAS1+ cell density does not change substantially throughout adult life, ranging from 30 to 90 cells/mm2.

“However, in contrast to the white matter, the cell density did not change substantially, ranging from 30 to 90 cells/mm2 throughout adult life (Fig. 5, E and F).”

Partially remyelinated lesions, as shown by pale myelin staining at the borders of the lesions, contain clusters of BCAS1+ oligodendrocytes.

“In contrast, partially remyelinated lesions, as shown by the pale myelin staining at the borders of the lesions, contained clusters of BCAS1+ oligodendrocytes (Fig. 7, A to E).”

BCAS1+ cells displayed multiple, symmetrically radiating processes or segments aligned in parallel closely resembling the morphology observed in mice.

“We found that BCAS1+ cells displayed multiple, symmetrically radiating processes or segments aligned in parallel closely resembling the morphology observed in mice.”

EGFP signal intensity increased with time in the corpus callosum and somatosensory cortex in PLP-CreERT2 reporter mice.

“We followed these animals for up to 12 months of age and found an increase in EGFP signal intensity with time in corpus callosum and somatosensory cortex (fig. S10, A to D).”

The number of BCAS1+ cells correlates with the established typical chronological sequence of myelination in the white matter.

“In addition, the number of BCAS1+ cells correlated with the established typical chronological sequence of myelination in the white matter”

• AssumptionRests on an assumption: The typical chronological sequence of myelination in the human white matter is established.

Completely demyelinated chronic lesions in the white matter only rarely contain BCAS1+ oligodendrocytes.

“We found that completely demyelinated chronic lesions in the white matter only rarely contained BCAS1+ oligodendrocytes (Fig. 7A and fig. S13A)”

The number of GFP+ oligodendrocytes labeled 18 days after tamoxifen injection did not change over the 11 months of chase.

“When we quantified the density of GFP+ cells in the somatosensory cortex of tamoxifen-treated transgenic animals, we found that the number of GFP+ oligodendrocytes labeled 18 days after tamoxifen injection did not change over the 11 months of chase, suggesting that developmentally born myelinating oligodendrocytes survive into late adulthood and expand their myelin sheaths (fig. S10, E and F).”

At 1 year of age, abundant BCAS1+ myelin sheaths are observed in the white and gray matter.

“At 1 year of age, abundant BCAS1+ myelin sheaths were observed in the white and gray matter (Fig. 5D and fig. S12)”

The capacity to generate or maintain BCAS1+ oligodendrocytes is retained until old age in MS patients up to 74 years of age.

“Our analysis of MS lesions from patients up to 74 years of age showed that the capacity to generate or maintain BCAS1+ oligodendrocytes is retained until old age (table S2).”

In the human frontal cortex, BCAS1+ oligodendrocyte densities are highest during developmental myelination in adolescence and young adulthood.

“We therefore determined the number of BCAS1+ oligodendrocytes in the human frontal cortex and found the highest densities during developmental myelination in adolescence and young adulthood (Fig. 5, E and F).”

65 ± 2.7% of BCAS1+ cells incorporated EdU after 10 days of EdU administration in 4-month-old mice.

“When EdU was administered for 10 days via the drinking water to 4-month-old mice, 65 ± 2.7% of the BCAS1+ cells incorporated EdU (Fig. 3B).”

After 40 days of chase only, 7.7 ± 1.3% of the EdU+/BCAS1+ cells were left.

“Notably, after 40 days of a “chase” only, 7.7 ± 1.3% of the EdU+/BCAS1+ cells were left revealing their transient nature (Fig. 3B).”

BCAS1+ myelinating oligodendrocyte density in the frontal cortex was 206.4 ± 57.8 cells/mm3 at 7 months.

“BCAS1+ myelinating oligodendrocytes were found at a density of 715.5 ± 66.8 cells/mm3 in young (P40) mice and remained as an abundant cell population in the adult mice (4 and 7 months of age), where they were found in the somatosensory cortex at a density of 379 ± 11.9 cells/mm3 (4 months) and 347.7 ± 26.6 cells/mm3 (7 months; Fig. 4A) and in the frontal cortex at a density of206.4 ± 57.8 cells/mm”

In newborn human autopsy cases (n = 3), BCAS1+ cells displayed multiple and branched processes.

“When newborn human autopsy cases (n = 3) were stained with BCAS1 antibodies, we observed, as in mice, cells with multiple and branched processes (Fig. 5A).”

After 5 days in culture, when oligodendrocytes formed sheets and expressed MBP, BCAS1 immunolabeling was reduced.

“However, after 5 days in culture, when oligodendrocytes formed sheets and expressed MBP, we observed a reduction in BCAS1 immunolabeling (fig. S5B).”

The number of EdU+/CC1+/BCAS1+ cells decreased with time.

“The number of EdU+/CC1+/BCAS1+cells, however, decreased with time, confirming our conclusion of their transient nature (Fig. 3D).”

Only 4 ± 1.2% of fully mature MBP+ oligodendrocytes were labeled with antibodies against BCAS1 at 32 days in vitro.

“We found that only 4 ± 1.2% of the fully mature MBP+ oligodendrocytes were labeled with antibodies against BCAS1 (fig. S7B), demonstrating the enrichment of BCAS1 at an early differentiation stage in both mouse- and human-cultured oligodendrocytes.”

BCAS1 expression is lost when oligodendrocytes mature into later stages of oligodendrocyte differentiation.

“However, when the analysis was performed at P14, a population of GFP+ myelinating oligodendrocytes that lacked BCAS1 expression emerged (Fig. 2, E and F), suggesting that BCAS1 expression is lost when oligodendrocytes mature into later stages of oligodendrocyte differentiation (Fig. 2, G and H).”

BCAS1+ cells differentiate from oligodendrocyte progenitor cells.

“When we analyzed the progenies of the labeled cells at 7, 18, and 40 days after injection by immunostaining, we observed an increase in the number of cells co-expressing BCAS1 and GFP from days 7 to 18 in the somatosensory cortex, indicating that BCAS1+ cells differentiate from oligodendrocyte progenitor cells (Fig. 1D).”

BCAS1 presents a potential cellular target for remyelination therapies in MS.

“Our work identifies a means to map ongoing myelin formation in health and disease and presents a potential cellular target for remyelination therapies in MS.”

• AssumptionRests on an assumption: Human studies of white matter changes upon learning and training are often based on magnetic resonance imaging, which does not provide direct information on myelin.

BCAS1+ cells with segments aligned in parallel are myelin-forming oligodendrocytes.

“The ensheathment of axons together with the formation of axon-glial paranodal junctions define the BCAS1+ cells with segments aligned in parallel as myelin-forming oligodendrocytes.”

BCAS1+ cells are newly formed, myelinating oligodendrocytes.

“These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult.”

The work identifies a means to map ongoing myelin formation in health and disease.

“Our work identifies a means to map ongoing myelin formation in health and disease and presents a potential cellular target for remyelination therapies in MS.”

• AssumptionRests on an assumption: No molecular marker exists that allows discrimination of myelinated from remyelinated axons, and ongoing myelination is difficult to detect, so it has not been possible to determine whether new myelin sheaths are formed in chronically demyelinated MS lesions.

BCAS1+ cells segregate from oligodendrocyte progenitor cells and mature oligodendrocytes.

“These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult.”

• Also stated in: § BCAS1+ premyelinating and myelinating oligodendrocytes are present during development and in adult mice · plain

  “Thus, BCAS1+ cells represent a population of oligodendrocytes that are at an intermediate state of differentiation, segregating from both oligodendrocyte progenitor cells and mature oligodendrocytes.”

The anti-BCAS1 antibody specifically detects BCAS1.

“We generated a polyclonal antibody (see Supplementary Materials for details) against BCAS1 and validated its specificity by preabsorption of the antibody with recombinant BCAS1 protein before immunolabeling. Preabsorption eliminated staining of mouse brain sections (fig. S1A).”

• Also stated in: § BCAS1 expression identifies newly generated oligodendrocytes · boosted

  “Finally, abolished BCAS1 immunoreactivity on adult Bcas1 knockout mouse brain sections demonstrated that the staining was specific for BCAS1 (fig. S1D).”

PLP+ premyelinating oligodendrocytes constitute a subpopulation present only during development.

“When the analysis was performed in the adult somatosensory cortex (at 4 months), we found that all BCAS1+ premyelinating oligodendrocytes were negative for GFP, suggesting that the previously identified PLP+ premyelinating oligodendrocytes constitute a subpopulation (29.5 ± 8.1% at P9,23.7 ± 1.7% at P14, and 0% at 4 months) of oligodendrocytes present only during development (Fig. 2B).”

BCAS1+ cells might be useful for identifying active myelination.

“suggesting that these cells might be useful for identifying active myelination.”

The generation of new myelin sheaths in the adult is likely due to a maturation or adaptive process that continues into adulthood in mice.

“Hence, these results do not support an extensive turnover of myelinating oligodendrocytes but rather suggest that the generation of new myelin sheaths in the adult is likely due to a maturation or adaptive process that continues into adulthood in mice.”

A proportion of BCAS1+ oligodendrocytes are engaged in actively reforming myelin in human MS lesions.

“suggesting that a proportion of these cells are engaged in actively reforming myelin.”

BCAS1+ cells are segregated from other known oligodendroglial subpopulations.

“demonstrating that BCAS1+ cells are segregated from other known oligodendroglial subpopulations.”

BCAS1+ cells are likely to represent myelinating oligodendrocytes.

“further suggesting that BCAS1+ cells are likely to represent myelinating oligodendrocytes.”

BCAS1 is enriched at an early differentiation stage in both mouse- and human-cultured oligodendrocytes.

“We found that only 4 ± 1.2% of the fully mature MBP+ oligodendrocytes were labeled with antibodies against BCAS1 (fig. S7B), demonstrating the enrichment of BCAS1 at an early differentiation stage in both mouse- and human-cultured oligodendrocytes.”

Remyelination starts at the lesion border in the white matter.

“suggesting that remyelination starts at the lesion border in the white matter (Fig. 7, A to H).”

BCAS1 immunoreactivity identifies a unique stage of oligodendrocyte differentiation in the human brain.

“We therefore concluded that BCAS1 immunoreactivity identifies a unique stage of oligodendrocyte differentiation in the human brain.”

The results do not support an extensive turnover of myelinating oligodendrocytes.

“Hence, these results do not support an extensive turnover of myelinating oligodendrocytes but rather suggest that the generation of new myelin sheaths in the adult is likely due to a maturation or adaptive process that continues into adulthood in mice.”

These results point to the possibility of adult adaptive myelination in the human frontal cortex.

“These results contrast with the white matter tracts and point to the possibility of adult adaptive myelination in the human frontal cortex.”

BCAS1+ cells might represent myelinating oligodendrocytes.

“suggesting that BCAS1+ cells might represent myelinating oligodendrocytes.”

BCAS1+ cells are transient in the corpus callosum.

“Notably, after 40 days of a “chase” only, 7.7 ± 1.3% of the EdU+/BCAS1+ cells were left revealing their transient nature (Fig. 3B).”

At least some BCAS1+ cells are actively engaged in forming myelin in MS lesions.

“the observation that BCAS1+ cells are associated with partially remyelinated lesions suggests that at least some of these cells are actively engaged in forming myelin.”

Active remyelination at the lesion edge is ongoing in a proportion of established, fully demyelinated MS lesions, even at advanced stages of the disease.

“Our work suggests that active remyelination at the lesion edge is ongoing in a proportion of established, fully demyelinated MS lesions, even at advanced stages of the disease.”