Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function
| Autor: | Brahmananda R. Chitteti, Sonia Rodriguez-Rodriguez, W. Scott Goebel, Ying Hua Cheng, Edward F. Srour, Bradley Poteat, Melissa A. Kacena, Nadia Carlesso |
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| Rok vydání: | 2010 |
| Předmět: |
Stromal cell
Hematopoiesis and Stem Cells Cellular differentiation Immunology Notch signaling pathway Cell Communication Cell Separation Biology Biochemistry Mice Bone Marrow medicine Animals Stem Cell Niche Progenitor cell Notch 2 Cells Cultured Cell Proliferation Mice Knockout Osteoblasts Receptors Notch Reverse Transcriptase Polymerase Chain Reaction Cell Differentiation Cell Biology Hematology Flow Cytometry Hematopoietic Stem Cells Coculture Techniques Hematopoiesis Cell biology Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure Bone marrow Stromal Cells Stem cell Signal Transduction |
| Zdroj: | Blood. 115:3239-3248 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Hematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic and extrinsic parameters. We examined the impact of hematopoietic niche elements on HSC and HPC function by analyzing the combined effect of osteoblasts (OBs) and stromal cells (SCs) on Lineage−Sca-1+CD117+ (LSK) cells. CFU expansion and marrow repopulating potential of cultured Lineage−Sca-1+CD117+ cells were significantly higher in OB compared with SC cultures, thus corroborating the importance of OBs in the competence of the hematopoietic niche. OB-mediated enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs, suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity. Although the suppressive effect of SC was mediated by adipocytes, probably through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1 and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not segregate the hematopoiesis-enhancing activity but demonstrated that this function is common to OBs from different anatomic sites. These data illustrate that OBs promote in vitro maintenance of hematopoietic functions, including repopulating potential by up-regulating Notch-mediated signaling between HSCs and OBs. |
| Databáze: | OpenAIRE |
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