Companion Blood Cells Control Ovarian Stem Cell Niche Microenvironment and Homeostasis

Abstract

The extracellular matrix plays an essential role for stem cell differentiation and niche homeostasis. Yet, the origin and mechanism of assembly of the stem cell niche microenvironment remain poorly characterized. Here, we uncover an association between the niche and blood cells, leading to the formation of the Drosophila ovarian germline stem cell niche basement membrane. We identify a distinct pool of plasmatocytes tightly associated with the developing ovaries from larval stages onward. Expressing tagged collagen IV tissue specifically, we show that the germline stem cell niche basement membrane is produced by these "companion plasmatocytes" in the larval gonad and persists throughout adulthood, including the reproductive period. Eliminating companion plasmatocytes or specifically blocking their collagen IV expression during larval stages results in abnormal adult niches with excess stem cells, a phenotype due to aberrant BMP signaling. Thus, local interactions between the niche and blood cells during gonad development are essential for adult germline stem cell niche microenvironment assembly and homeostasis.

Macrophages and cellular immunity in Drosophila melanogaster

“…This suggests that at least some, if not all, plasmatocytes have lineage-restricted progenitor capacity, underscoring further parallels with vertebrate EMPs [31]. Several studies have reported distinct subpopulations of plasmatocytes with varying combinations [37, 38], and quantitative expression differences [17], of commonly used plasmatocyte “markers” such as Hemolectin [39], Peroxidasin [40], P1 (Nimrod C1) [41], Croquemort [42], Eater [43], and the pan-hemocyte marker Hemese [44]. This favors the idea that specialized subsets of plasmatocytes exist, which could reflect distinct functional capabilities of these cells.…”

“…From this point onward, the two blood cell lineages intermix, and distinguishing embryonic and Lymph Gland hemocytes is, according to current methodology, only possible by lineage tracing. In the adult, plasmatocytes reside in or close to a number of tissues, including fat body (which regulates metabolism and immunity), heart, respiratory (tracheal) system, gut, peripheral nervous system, and ovaries ([38, 91–96] and Brückner lab in preparation). In addition, small numbers of crystal cells, but no lamellocytes, are present in the adult [2, 92, 97].…”

“…A recent report claimed de novo production of hemocytes in the adult fly [92], whereas the majority of studies have not been able to obtain evidence of proliferation in adult hemocyte populations [2, 38, 97, 102], even under a range of immune-challenged conditions (Brückner lab in preparation). Indeed immunosenescence, involving a decline in both hemocyte number and phagocytic function, has been documented as adult flies age [101].…”

“…During larval development, hemocytes associate with the female gonad and secrete the ECM molecule Collagen IV (ColIV) [38]. These layers of ColIV are required during pupariation and adulthood to ensure proper molecular function of the germline stem cell niche, and in turn, germline stem cell number and homeostasis [38]. The possibility that macrophages regulate other stem cell microenvironments is tantalizing, and will be interesting to explore in the future.…”

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging

“…Virant et al indicated that there is a potential connection between the VSELs and the germinal system as well as the hemapoiesis reconstruction process [59]. Veronique et al [60] found that the “companion” blood cells are essential for the formation and the steady state of the ovarian germ stem cell nests. Therefore, we can conclude that the circulatory system is important for promoting ovarian functions.…”