Histone deacetylases differentially regulate the proliferative phenotype of mouse bone marrow stromal and hematopoietic stem/progenitor cells

Neha R. Dhoke, Evangelene Kalabathula, Komal Kaushik, Ramasatyaveni Geesala, B. Sravani, Amitava Das

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Mouse bone marrow stromal stem/progenitor cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and Hematopoietic Stem and Progenitor Cells (HSPCs) with differential proliferative potentials were investigated for identifying epigenetic signals that can modulate their growth. In the present study, immunodepletion of granulo-monocytic (CD11b) and erythroid (Ter119) population yielded CD11b-/Ter119- cells, capable of differentiating into chondrogenic, osteogenic and adipogenic cells. Enrichment of the CD11b+ population by positive selection of multipotent stem/progenitor marker (CD133) yielded CD11b+/CD133+ cells, efficiently differentiated into hematopoietic lineages. Molecular characterization revealed the expression of BMSC and HSPC markers in CD11b-/Ter119- and CD11b+/CD133+ sorted populations, respectively. Cell expansion studies depicted a higher growth rate and percentage of proliferating cells in G2/M phase of cell cycle in BMSCs (13.9 ± 2.9%) as compared with HSPCs (5.8 ± 0.8%). Analysis of the HDACs gene expression revealed a differential expression pattern in BMSCs and HSPCs that modulates the cell cycle genes. Trichostatin A (TSA)-mediated HDAC inhibition led to an increased level of AcH3 and AcH4 along with cyclins B1 and D2. Chromatin immunoprecipitation revealed alleviation of HDAC2 and HDAC3 binding by TSA on cyclins B1 and D2 promoter, thereby enhancing cell proliferation. This study identifies epigenetic modulation on the proliferative potential of BMSCs and HSPCs for stem cell transplantation therapies.

Original languageEnglish (US)
Pages (from-to)170-180
Number of pages11
JournalStem Cell Research
Volume17
Issue number1
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
AD acknowledges the funding provided by “ CSIR-Mayo Clinic for Innovation and Translational Research , CKM-CMPP-07 ” and CSIR, Ministry of Science and Technology, Government of India, XIIth Five-year Plan Project # CSC-0111. Fellowships provided by ICMR and UGC are gratefully acknowledged by ND (ICMR-SRF), KK (UGC-JRF) and RG (UGC-SRF). We also thank the technical assistance provided by Mr. Suresh Y in assisting the Flow-cytometry analysis and confocal imaging.

Publisher Copyright:
© 2016.

Keywords

  • BMSCs
  • Cyclin B1
  • Cyclin D2
  • HDAC2
  • HDAC3
  • HSPCs

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