OUR DATA
Mesenchymal precursor cells in adult nerves contribute to mammalian tissue repair and regeneration
Matthew J. Carr, Jeremy S. Toma, Adam P.W. Johnston, Patrick E Steadman, Scott A. Yuzwa, Neemat Mahmud, Paul W. Frankland, David R. Kaplan, Freda D. Miller. Cell Stem Cell, 2019.
Peripheral innervation plays an important role in regulating tissue repair and regeneration. Here, we provide evidence that injured peripheral nerves provide a reservoir of mesenchymal precursor cells that can directly contribute to murine digit tip regeneration and skin repair. In particular, using single-cell RNA sequencing and lineage tracing we identify transcriptionally-distinct mesenchymal cell populations within the control and injured adult nerve, including neural crest-derived cells in the endoneurium with characteristics of mesenchymal precursor cells. Culture and transplantation studies show that these nerve-derived mesenchymal cells have the potential to differentiate into non-nerve lineages. Moreover, following digit tip amputation, the neural crest-derived nerve mesenchymal cells contribute to the regenerative blastema and ultimately to the regenerated bone. Similarly, neural crest derived nerve mesenchymal cells contribute to the dermis during skin wound healing. These findings support a model where peripheral nerves directly contribute mesenchymal precursor cells to promote repair and regeneration of injured mammalian tissues.
Raw single-cell RNA seq datasets
Processed single-cell RNA seq datasets and visualization packages
Single-Cell Profiling Shows Murine Forebrain Neural Stem Cells Reacquire a Developmental State when Activated for Adult Neurogenesis
Michael J. Borrett, Brendan T. Innes, Danielle Jeong, Nareh Tahmasian, Mekayla A. Storer, Gary D. Bader, David R. Kaplan, and Freda D. Miller. Cell Reports, 2020
The transitions from developing to adult quiescent and activated neural stem cells (NSCs) are not well understood. Here, we use single-cell transcriptional profiling and lineage tracing to characterize these transitions in the murine forebrain. We show that the two forebrain NSC parental populations, embryonic cortex and ganglionic eminence radial precursors (RPs), are highly similar even though they make glutamatergic versus gabaergic neurons. Both RP populations progress linearly to transition from a highly active embryonic to a dormant adult stem cell state that still shares many similarities with embryonic RPs. When adult NSCs of either embryonic origin become reactivated to make gabaergic neurons, they acquire a developing ganglionic eminence RP-like identity. Thus, transitions from embryonic RPs to adult NSCs and back to neuronal progenitors do not involve fundamental changes in cell identity, but rather reflect conversions between activated and dormant NSC states that may be determined by the niche environment.
Table 1: Gene sets positively correlated with embryonic RPs versus adult dNSCs in ICA component 1. Related to Figure 7. Shown are gene sets that are positively correlated with embryonic RPs relative to adult dNSCs in ICA component 1 where FDR < 0.01. Also shown are adjusted p values (adj p value), enrichment scores (Norm. Enr. Score), the size of the gene set and the number of times a random gene set had a more extreme enrichment score than the gene set (nMoreExtreme). Gene sets are ordered from most to least significant from top to bottom. These gene sets were also categorized with regard to a number of broad categories, including DNA replication, DNA repair, chromosome stability and segregation and the cell cycle (yellow), transcription, epigenetics and chromatin regulation (blue), RNA homeostasis, translation and tRNA and ribosome biogenesis (orange), general protein metabolism and trafficking including ubiquitination and sumoylation (green) and signaling pathways (red). IR indicates they were not considered relevant to the NSCs, and Miscellaneous includes gene sets that do not fit into these categories.
Table 2: Gene sets negatively correlated with embryonic RPs versus adult dNSCs in ICA component 1. Related to Figure 7. Shown are gene sets that are negatively correlated with embryonic RPs versus adult dNSCs (that is, higher in adult dNSCs) in ICA component 1 as shown in the top volcano plot in Fig. 7F. Also shown are adjusted p values (Adj. p value), enrichment scores (Norm. Enr. Score), the size of the gene set and the number of times a random gene set had a more extreme enrichment score than the gene set (nMoreExtreme). Gene sets are ordered from most to least significant from top to bottom. These gene sets were also categorized with regard to a number of broad categories, including environmental sensing (yellow), metabolism (orange), extracellular matrix (blue) and plasma membrane (green). IR indicates they were not considered relevant to the NSCs and Miscellaneous includes gene sets that do not fit into these categories.
Table 3: Gene sets negatively correlated with embryonic GE RPs versus cortical RPs in ICA component 11. Related to Figure 7. Shown are gene sets that are negatively correlated with E14 GE RPs relative to E14 cortical RPs (that is, higher in cortical RPs) in ICA component 11 as shown in the bottom volcano plot in Fig. 7F. Also shown are adjusted p values (Adj. p value), enrichment scores (Norm. Enr. Score), the size of the gene set and the number of times a random gene set had a more extreme enrichment score than the gene set (nMoreExtreme). Gene sets are ordered from most to least significant from top to bottom.
Table 4: Gene sets positively correlated with embryonic GE RPs versus cortical RPs in ICA component 11. Related to Figure 7. Shown are gene sets that are positively correlated with E14 GE RPs relative to E14 cortical RPs in ICA component 11 as shown in the bottom volcano plot in Fig. 7F. Also shown are adjusted p values (Adj. p value), enrichment scores (Norm. Enr. Score), the size of the gene set and the number of times a random gene set had a more extreme enrichment score than the gene set (nMoreExtreme). Gene sets are ordered from most to least significant from top to bottom.