Identification of a human adult cardiac stem cell population with neural crest origin

Höving, A. L.; Merten, M.; Schmidt, K. E.; Faust, I.; Ruiz-Perera, L. M.; Hachmeister, H.; Sommer, S.-P.; Fujita, B.; Pühler, T.; Huser, T.; Greiner, J. F. W.; Kaltschmidt, B.; Gummert, J.; Knabbe, C.; Kaltschmidt, C.

doi:10.1101/590679

bioRxiv · 10.1101/590679

Identification of a human adult cardiac stem cell population with neural crest origin

Höving, A. L.·Merten, M.·Schmidt, K. E.·Faust, I.·Ruiz-Perera, L. M.·Hachmeister, H.·Sommer, S.-P.·Fujita, B.·Pühler, T.·Huser, T.·Greiner, J. F. W.·Kaltschmidt, B.·Gummert, J.·Knabbe, C.·Kaltschmidt, C.

View original source ↗Export metadata ↓

Abstract

Cardiovascular diseases are the major cause of death worldwide, emphasizing the necessity to better understand adult human cardiac cell biology and development. Although the adult heart was considered as a terminally differentiated organ, rare populations of cardiac stem cells (CSCs) have been described so far, with their developmental origin and endogenous function still being a matter of debate.\n\nHere, we identified a Nestin+/S100+/CD105+/Sca1+/cKit- population of CSCs in the myocardium of the adult human heart auricle. Isolated cells showed expression of characteristic neural crest-derived stem cell (NCSC) markers and kept their genetic stability during cultivation in vitro. Cultivated hCSCs efficiently gave rise to functional, beating cardiomyocytes, osteoblasts, adipocytes and neurons. Global transcriptome analysis via RNAseq showed a high similarity between the expression profiles of Nestin+/S100+/CD105+/Sca1+/cKit- hCSCs and adult human NCSCs from the nasal cavity (inferior turbinate stem cells, ITSCs). In detail, 88.1 % of all genes were significantly expressed in both stem cell populations particularly including common NCSC-markers. Based on these observations, we suggest a similar developmental origin of both stem cell populations.\n\nIn summary, we identified a human adult cardiac stem cell population with neural crest-origin, which may also contribute to endogenous cardiac tissue homeostasis and tissue repair in vivo.

Explore related subjects

cell biology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Höving, A. L., Merten, M., Schmidt, K. E., Faust, I., Ruiz-Perera, L. M., Hachmeister, H., Sommer, S.-P., Fujita, B., Pühler, T., Huser, T., Greiner, J. F. W., Kaltschmidt, B., Gummert, J., Knabbe, C., Kaltschmidt, C.. 2019-03-27. Identification of a human adult cardiac stem cell population with neural crest origin. https://doi.org/10.1101/590679

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A dynamic phosphoproteome reveals stage-specific regulation of cytokinesis in Leishmania

Leishmania parasites undergo extensive morphological and metabolic remodelling during their transition from motile insect promastigotes to non-motile intracellular amastigotes, yet how dynamic protein kinase signalling drives this process remains poorly understood. Here, we present a high-resolution temporal phosphoproteome of L. mexicana promastigote to axenic amastigote differentiation, profiling 16,495 phosphosites on 3,101 proteins across seven developmental time points and identifying 5,795 dynamically regulated sites. This temporal map reveals stage-specific signalling programs, including regulated sites in MPK2 and non-regulated sites in MRK1, protein kinases known to be essential for amastigote differentiation. Using analogue-sensitive (AS) chemical genetics, we show that acute inhibition of either kinase in axenic amastigotes disrupts the spatial coordination of cleavage furrow ingression with nuclear and kinetoplast segregation, revealing essential cytokinesis roles obscured in constitutive gene deletions. Despite generating similar cytokinesis phenotypes, genetic over-expression and cellular localisation analyses demonstrate that MPK2 and MRK1 act through spatially segregated signalling pathways. Time-resolved phosphoproteomics upon MPK2 inhibition places its activity upstream of cytoskeletal remodelling networks. Importantly, we show that the stage-specific requirement for MPK2 is defined by the parasite's morphology: while motile promastigotes tolerate MPK2 inhibition, genetic ablation of flagellar motility sensitises them to loss of MPK2 activity. Thus, flagellar motility acts as a mechanical buffer during promastigote division, explaining why non-motile amastigotes are vulnerable to MPK2 inhibition. Together, our findings provide a systems level framework for Leishmania signalling and demonstrate that cellular architecture and biomechanics dictate protein kinase dependency across developmental stages of the parasite.

cell biology↗

bioRxiv2026

Single-cell Transcriptome-Proteome-PTMome(x8)-Metabolome (scTPPM) co-profiling decodes multimodal regulation during mouse oocyte meiosis

Single-cell multi-omics technology is crucial for comprehensive characterization of cellular molecular features. Despite recent advances in single-cell multi-omics approaches, co-profiling of nucleic acids, proteins, metabolites, and post-translational modifications (PTMs) within the same cell individuals remains major challenges. Here, we developed a single-cell transcriptome, proteome, PTMome, and metabolome (scTPPM) profiling approach, enabling simultaneous analysis of transcriptomes, proteomes, eight types of PTMs (e.g., phosphorylation, methylation, ubiquitination, O_GlcNAc, acetylation, crotonylation, lactylation, and succinylation), and metabolomes in individual cells. We demonstrated the scTPPM's performance in tumor cell lines and oocyte samples, reaching total identification and quantification of 27,668 genes, 4,847 proteins, 1,508 PTM sites, and 680 metabolites in single mouse oocytes. We profiled previously-uncharacterized dynamic crosstalk among the entire metabolic pathways from metabolic enzyme expression and regulation to metabolite-mediated post-translational modifications during oocyte maturation. In summary, scTPPM provided an effective workflow for multi-omics co-profiling in single cells, enabling multi-layered insights into complex regulatory network.

cell biology↗

bioRxiv2026

Sequence context and partner availability specify divergent cell fates from a single transcription factor

Transcription factors drive the gene regulatory networks that control developmental transitions, yet which of their many targets a cell uses remains unresolved. Expressing Cebp, Cebp{beta} or Cebp{delta} identically, alone or with Oct4, Sox2, Klf4 and cMyc, gave four outcomes: adipocyte from fibroblasts and neural stem cells, trophectoderm from embryonic stem cells, and myeloid from B cells. Raising Cebp levels changed how many sites it reached, not which sequence it read: clustered motifs maintained somatic enhancers, while spillover onto low-copy sites created de novo enhancers carrying composites of Cebp and cell-type-restricted partners. In fibroblasts, Cebp also redistributed Oct4, Sox2 and Klf4 from early targets, blocking iPSC formation. Supplying the predicted partners rewrote the output: Spi1 redirected Cebp into parallel adipogenic and myeloid programs, via a transient PpargCD45 state using separate enhancers for each; TFAP2C abolished adipogenic conversion. Motif density and partner composites therefore assemble a factor's instructive output in the receiving cell.

cell biology↗